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Database: PDB
Entry: 2VIO
LinkDB: 2VIO
Original site: 2VIO 
HEADER    HYDROLASE                               05-DEC-07   2VIO              
TITLE     FRAGMENT-BASED DISCOVERY OF MEXILETINE DERIVATIVES AS ORALLY          
TITLE    2 BIOAVAILABLE INHIBITORS OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR      
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: UROKINASE-TYPE PLASMINOGEN ACTIVATOR CHAIN B;              
COMPND   3 CHAIN: A;                                                            
COMPND   4 FRAGMENT: CATALYTIC DOMAIN, RESIDUES 179-431;                        
COMPND   5 SYNONYM: UROKINASE-TYPE PLASMINOGEN ACTIVATOR, UPA, U-PLASMINOGEN    
COMPND   6 ACTIVATOR;                                                           
COMPND   7 EC: 3.4.21.73;                                                       
COMPND   8 ENGINEERED: YES;                                                     
COMPND   9 MUTATION: YES                                                        
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 EXPRESSION_SYSTEM: ESCHERICHIA COLI;                                 
SOURCE   6 EXPRESSION_SYSTEM_TAXID: 562                                         
KEYWDS    PLASMINOGEN ACTIVATION, EGF-LIKE DOMAIN, BLOOD COAGULATION,           
KEYWDS   2 INHIBITOR, POLYMORPHISM, GLYCOPROTEIN, FIBRINOLYSIS, KRINGLE,        
KEYWDS   3 ZYMOGEN, SECRETED, PROTEASE, HYDROLASE, UROKINASE-TYPE PLASMINOGEN   
KEYWDS   4 ACTIVATOR, PHARMACEUTICAL, SERINE PROTEASE, PHOSPHORYLATION          
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    M.FREDERICKSON,O.CALLAGHAN,G.CHESSARI,M.CONGREVE,S.R.COWAN,           
AUTHOR   2 J.E.MATTHEWS,R.MCMENAMIN,D.SMITH,M.VINKOVIC,N.G.WALLIS               
REVDAT   3   05-JUL-17 2VIO    1       REMARK                                   
REVDAT   2   24-FEB-09 2VIO    1       VERSN                                    
REVDAT   1   22-JAN-08 2VIO    0                                                
JRNL        AUTH   M.FREDERICKSON,O.CALLAGHAN,G.CHESSARI,M.CONGREVE,S.R.COWAN,  
JRNL        AUTH 2 J.E.MATTHEWS,R.MCMENAMIN,D.SMITH,M.VINKOVIC,N.G.WALLIS       
JRNL        TITL   FRAGMENT-BASED DISCOVERY OF MEXILETINE DERIVATIVES AS ORALLY 
JRNL        TITL 2 BIOAVAILABLE INHIBITORS OF UROKINASE-TYPE PLASMINOGEN        
JRNL        TITL 3 ACTIVATOR                                                    
JRNL        REF    J.MED.CHEM.                   V.  51   183 2008              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   18163548                                                     
JRNL        DOI    10.1021/JM701359Z                                            
REMARK   2                                                                      
REMARK   2 RESOLUTION.    1.80 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : BUSTER-TNT 2.1.1                                     
REMARK   3   AUTHORS     : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,              
REMARK   3               : PACIOREK,ROVERSI,SMART,VONRHEIN,WOMACK,              
REMARK   3               : MATTHEWS,TEN EYCK,TRONRUD                            
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 1.80                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 27.66                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 88.4                           
REMARK   3   NUMBER OF REFLECTIONS             : 19595                          
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT.                                     
REMARK   3   CROSS-VALIDATION METHOD           : THROUGHOUT                     
REMARK   3   FREE R VALUE TEST SET SELECTION   : RANDOM                         
REMARK   3   R VALUE     (WORKING + TEST SET)  : 0.192                          
REMARK   3   R VALUE            (WORKING SET)  : 0.189                          
REMARK   3   FREE R VALUE                      : 0.250                          
REMARK   3   FREE R VALUE TEST SET SIZE   (%)  : 5.000                          
REMARK   3   FREE R VALUE TEST SET COUNT       : 987                            
REMARK   3   ESTIMATED ERROR OF FREE R VALUE   : NULL                           
REMARK   3                                                                      
REMARK   3  FIT IN THE HIGHEST RESOLUTION BIN.                                  
REMARK   3   TOTAL NUMBER OF BINS USED               : NULL                     
REMARK   3   BIN RESOLUTION RANGE HIGH   (ANGSTROMS) : NULL                     
REMARK   3   BIN RESOLUTION RANGE LOW    (ANGSTROMS) : NULL                     
REMARK   3   BIN COMPLETENESS (WORKING+TEST)     (%) : NULL                     
REMARK   3   REFLECTIONS IN BIN (WORKING + TEST SET) : NULL                     
REMARK   3   BIN R VALUE        (WORKING + TEST SET) : NULL                     
REMARK   3   REFLECTIONS IN BIN        (WORKING SET) : NULL                     
REMARK   3   BIN R VALUE               (WORKING SET) : NULL                     
REMARK   3   BIN FREE R VALUE                        : NULL                     
REMARK   3   BIN FREE R VALUE TEST SET SIZE      (%) : NULL                     
REMARK   3   BIN FREE R VALUE TEST SET COUNT         : NULL                     
REMARK   3   ESTIMATED ERROR OF BIN FREE R VALUE     : NULL                     
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 1952                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 19                                      
REMARK   3   SOLVENT ATOMS            : 271                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : NULL                           
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : NULL                           
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : NULL                                                 
REMARK   3    B22 (A**2) : NULL                                                 
REMARK   3    B33 (A**2) : NULL                                                 
REMARK   3    B12 (A**2) : NULL                                                 
REMARK   3    B13 (A**2) : NULL                                                 
REMARK   3    B23 (A**2) : NULL                                                 
REMARK   3                                                                      
REMARK   3  ESTIMATED COORDINATE ERROR.                                         
REMARK   3   ESD FROM LUZZATI PLOT                    (A) : NULL                
REMARK   3   DPI (BLOW EQ-10) BASED ON R VALUE        (A) : NULL                
REMARK   3   DPI (BLOW EQ-9) BASED ON FREE R VALUE    (A) : NULL                
REMARK   3   DPI (CRUICKSHANK) BASED ON R VALUE       (A) : NULL                
REMARK   3   DPI (CRUICKSHANK) BASED ON FREE R VALUE  (A) : NULL                
REMARK   3                                                                      
REMARK   3   REFERENCES: BLOW, D. (2002) ACTA CRYST D58, 792-797                
REMARK   3               CRUICKSHANK, D.W.J. (1999) ACTA CRYST D55, 583-601     
REMARK   3                                                                      
REMARK   3 CORRELATION COEFFICIENTS.                                            
REMARK   3   CORRELATION COEFFICIENT FO-FC      : NULL                          
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : NULL                          
REMARK   3                                                                      
REMARK   3   NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15                    
REMARK   3   TERM                          COUNT    WEIGHT   FUNCTION.          
REMARK   3    BOND LENGTHS              : NULL   ; NULL   ; NULL                
REMARK   3    BOND ANGLES               : NULL   ; NULL   ; NULL                
REMARK   3    TORSION ANGLES            : NULL   ; NULL   ; NULL                
REMARK   3    TRIGONAL CARBON PLANES    : NULL   ; NULL   ; NULL                
REMARK   3    GENERAL PLANES            : NULL   ; NULL   ; NULL                
REMARK   3    ISOTROPIC THERMAL FACTORS : NULL   ; NULL   ; NULL                
REMARK   3    BAD NON-BONDED CONTACTS   : NULL   ; NULL   ; NULL                
REMARK   3    IMPROPER TORSIONS         : NULL   ; NULL   ; NULL                
REMARK   3    PSEUDOROTATION ANGLES     : NULL   ; NULL   ; NULL                
REMARK   3    CHIRAL IMPROPER TORSION   : NULL   ; NULL   ; NULL                
REMARK   3    SUM OF OCCUPANCIES        : NULL   ; NULL   ; NULL                
REMARK   3    UTILITY DISTANCES         : NULL   ; NULL   ; NULL                
REMARK   3    UTILITY ANGLES            : NULL   ; NULL   ; NULL                
REMARK   3    UTILITY TORSION           : NULL   ; NULL   ; NULL                
REMARK   3    IDEAL-DIST CONTACT TERM   : NULL   ; NULL   ; NULL                
REMARK   3                                                                      
REMARK   3   RMS DEVIATIONS FROM IDEAL VALUES.                                  
REMARK   3    BOND LENGTHS                       (A) : NULL                     
REMARK   3    BOND ANGLES                  (DEGREES) : NULL                     
REMARK   3    PEPTIDE OMEGA TORSION ANGLES (DEGREES) : NULL                     
REMARK   3    OTHER TORSION ANGLES         (DEGREES) : NULL                     
REMARK   3                                                                      
REMARK   3  TLS DETAILS                                                         
REMARK   3   NUMBER OF TLS GROUPS  : NULL                                       
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 2VIO COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 05-DEC-07.                  
REMARK 100 THE DEPOSITION ID IS D_1290034670.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : NULL                               
REMARK 200  TEMPERATURE           (KELVIN) : 93                                 
REMARK 200  PH                             : 6.6                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : N                                  
REMARK 200  RADIATION SOURCE               : ROTATING ANODE                     
REMARK 200  BEAMLINE                       : NULL                               
REMARK 200  X-RAY GENERATOR MODEL          : RIGAKU RUH3R                       
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.5418                             
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : OSMIC BLUE CONFOCAL OPTICS         
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : CCD                                
REMARK 200  DETECTOR MANUFACTURER          : RIGAKU CCD                         
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : D*TREK                             
REMARK 200  DATA SCALING SOFTWARE          : D*TREK                             
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 19595                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 1.800                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 27.660                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : 0.000                              
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 88.4                               
REMARK 200  DATA REDUNDANCY                : 2.500                              
REMARK 200  R MERGE                    (I) : 0.09000                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : NULL                               
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.80                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 1.86                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 46.8                               
REMARK 200  DATA REDUNDANCY IN SHELL       : NULL                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.40000                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 1.500                              
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: OTHER                        
REMARK 200 SOFTWARE USED: NULL                                                  
REMARK 200 STARTING MODEL: NONE                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NONE                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 32.58                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 1.84                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: PROTEIN WAS CRYSTALLIZED FROM 22-24%     
REMARK 280  PEG4000, 0.17M (NH4)2SO4, 15% GLYCEROL, 0.1M NA(CH3COO) PH=4.0;     
REMARK 280  THEN SOAKED IN 0.05M COMPOUND, 28% PEG4000, 0.29M HEPES PH=6.6,     
REMARK 280  5% GLYCEROL, PH 6.6                                                 
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 21                       
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -X+1/2,-Y,Z+1/2                                         
REMARK 290       3555   -X,Y+1/2,-Z+1/2                                         
REMARK 290       4555   X+1/2,-Y+1/2,-Z                                         
REMARK 290                                                                      
REMARK 290     WHERE NNN -> OPERATOR NUMBER                                     
REMARK 290           MMM -> TRANSLATION VECTOR                                  
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY TRANSFORMATIONS                            
REMARK 290 THE FOLLOWING TRANSFORMATIONS OPERATE ON THE ATOM/HETATM             
REMARK 290 RECORDS IN THIS ENTRY TO PRODUCE CRYSTALLOGRAPHICALLY                
REMARK 290 RELATED MOLECULES.                                                   
REMARK 290   SMTRY1   1  1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   1  0.000000  1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   1  0.000000  0.000000  1.000000        0.00000            
REMARK 290   SMTRY1   2 -1.000000  0.000000  0.000000       26.20200            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       40.74150            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       27.09200            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       40.74150            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       26.20200            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       27.09200            
REMARK 290   SMTRY3   4  0.000000  0.000000 -1.000000        0.00000            
REMARK 290                                                                      
REMARK 290 REMARK: NULL                                                         
REMARK 300                                                                      
REMARK 300 BIOMOLECULE: 1                                                       
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM                
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN                  
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON               
REMARK 300 BURIED SURFACE AREA.                                                 
REMARK 350                                                                      
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN           
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE                
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS          
REMARK 350 GIVEN BELOW.  BOTH NON-CRYSTALLOGRAPHIC AND                          
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.                               
REMARK 350                                                                      
REMARK 350 BIOMOLECULE: 1                                                       
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC                         
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC                  
REMARK 350 SOFTWARE USED: PQS                                                   
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A                                     
REMARK 350   BIOMT1   1  1.000000  0.000000  0.000000        0.00000            
REMARK 350   BIOMT2   1  0.000000  1.000000  0.000000        0.00000            
REMARK 350   BIOMT3   1  0.000000  0.000000  1.000000        0.00000            
REMARK 400                                                                      
REMARK 400 COMPOUND                                                             
REMARK 400 ENGINEERED RESIDUE IN CHAIN A, MET 214 TO ILE                        
REMARK 400 ENGINEERED RESIDUE IN CHAIN A, CYS 299 TO SER                        
REMARK 465                                                                      
REMARK 465 MISSING RESIDUES                                                     
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE                       
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)                
REMARK 465                                                                      
REMARK 465   M RES C SSSEQI                                                     
REMARK 465     ASN A   246                                                      
REMARK 465     GLY A   247                                                      
REMARK 465     LEU A   248                                                      
REMARK 465     ALA A   249                                                      
REMARK 465     LEU A   250                                                      
REMARK 470                                                                      
REMARK 470 MISSING ATOM                                                         
REMARK 470 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;           
REMARK 470 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;          
REMARK 470 I=INSERTION CODE):                                                   
REMARK 470   M RES CSSEQI  ATOMS                                                
REMARK 470     GLU A 245    CA   C    O    CB   CG   CD   OE1                   
REMARK 470     GLU A 245    OE2                                                 
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT                     
REMARK 500                                                                      
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.                            
REMARK 500                                                                      
REMARK 500  ATM1  RES C  SSEQI   ATM2  RES C  SSEQI           DISTANCE          
REMARK 500   O    HOH A  2039     O    HOH A  2072              2.19            
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: TORSION ANGLES                                             
REMARK 500                                                                      
REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS:            
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;               
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).                             
REMARK 500                                                                      
REMARK 500 STANDARD TABLE:                                                      
REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2)                    
REMARK 500                                                                      
REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI-           
REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400            
REMARK 500                                                                      
REMARK 500  M RES CSSEQI        PSI       PHI                                   
REMARK 500    GLN A  27       57.79   -143.65                                   
REMARK 500    VAL A  41      -60.51   -100.90                                   
REMARK 500    SER A  54     -155.64   -151.20                                   
REMARK 500    ASP A  97     -154.93    -92.14                                   
REMARK 500    TYR A 171     -101.25    -91.07                                   
REMARK 500    SER A 214      -57.48   -128.85                                   
REMARK 500    GLU A 244     -117.40   -144.72                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 700                                                                      
REMARK 700 SHEET                                                                
REMARK 700 DETERMINATION METHOD: DSSP                                           
REMARK 700 THE SHEETS PRESENTED AS "AA" IN EACH CHAIN ON SHEET RECORDS          
REMARK 700 BELOW IS ACTUALLY AN  8-STRANDED BARREL THIS IS REPRESENTED BY       
REMARK 700 A  9-STRANDED SHEET IN WHICH THE FIRST AND LAST STRANDS              
REMARK 700 ARE IDENTICAL.                                                       
REMARK 700 THE SHEETS PRESENTED AS "AB" IN EACH CHAIN ON SHEET RECORDS          
REMARK 700 BELOW IS ACTUALLY AN  7-STRANDED BARREL THIS IS REPRESENTED BY       
REMARK 700 A  8-STRANDED SHEET IN WHICH THE FIRST AND LAST STRANDS              
REMARK 700 ARE IDENTICAL.                                                       
REMARK 800                                                                      
REMARK 800 SITE                                                                 
REMARK 800 SITE_IDENTIFIER: AC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ACT A1245                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE L1O A1246                 
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 1C5X   RELATED DB: PDB                                   
REMARK 900 STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING,    
REMARK 900 SUB- MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR    
REMARK 900 RELATED ID: 1GJ9   RELATED DB: PDB                                   
REMARK 900 ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OFSER190    
REMARK 900 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS                            
REMARK 900 RELATED ID: 1W0Z   RELATED DB: PDB                                   
REMARK 900 UPA                                                                  
REMARK 900 RELATED ID: 1FV9   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF HUMAN MICROUROKINASE IN COMPLEX WITH 2-AMINO-5- 
REMARK 900 HYDROXY-BENZIMIDAZOLE                                                
REMARK 900 RELATED ID: 1VJA   RELATED DB: PDB                                   
REMARK 900 UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-JT464 COMPLEX                
REMARK 900 RELATED ID: 1GJ8   RELATED DB: PDB                                   
REMARK 900 ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OFSER190    
REMARK 900 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS                            
REMARK 900 RELATED ID: 1W11   RELATED DB: PDB                                   
REMARK 900 UPA                                                                  
REMARK 900 RELATED ID: 1SQO   RELATED DB: PDB                                   
REMARK 900 SUBSTITUTED 2-NAPHTHAMIDINE INHIBITORS OF UROKINASE                  
REMARK 900 RELATED ID: 1GJD   RELATED DB: PDB                                   
REMARK 900 ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OFSER190    
REMARK 900 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS                            
REMARK 900 RELATED ID: 1W10   RELATED DB: PDB                                   
REMARK 900 UPA                                                                  
REMARK 900 RELATED ID: 1OWK   RELATED DB: PDB                                   
REMARK 900 SUBSTITUTED 2-NAPHTHAMIDINE INHIBITORS OF UROKINASE                  
REMARK 900 RELATED ID: 1W12   RELATED DB: PDB                                   
REMARK 900 UPA                                                                  
REMARK 900 RELATED ID: 1GI9   RELATED DB: PDB                                   
REMARK 900 A NOVEL SERINE PROTEASE INHIBITION MOTIF INVOLVING A MULTI-CENTERED  
REMARK 900 SHORT HYDROGEN BONDING NETWORK AT THE ACTIVE SITE                    
REMARK 900 RELATED ID: 1O5A   RELATED DB: PDB                                   
REMARK 900 DISSECTING AND DESIGNING INHIBITOR SELECTIVITY DETERMINANTSAT THE    
REMARK 900 S1 SITE USING AN ARTIFICIAL ALA190 PROTEASE (ALA190UPA)              
REMARK 900 RELATED ID: 1C5Z   RELATED DB: PDB                                   
REMARK 900 STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING,    
REMARK 900 SUB- MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR    
REMARK 900 RELATED ID: 1OWJ   RELATED DB: PDB                                   
REMARK 900 SUBSTITUTED 2-NAPHTHAMIDINE INHIBITORS OF UROKINASE                  
REMARK 900 RELATED ID: 1GI7   RELATED DB: PDB                                   
REMARK 900 A NOVEL SERINE PROTEASE INHIBITION MOTIF INVOLVING A MULTI-CENTERED  
REMARK 900 SHORT HYDROGEN BONDING NETWORK AT THE ACTIVE SITE                    
REMARK 900 RELATED ID: 1O5B   RELATED DB: PDB                                   
REMARK 900 DISSECTING AND DESIGNING INHIBITOR SELECTIVITY DETERMINANTSAT THE    
REMARK 900 S1 SITE USING AN ARTIFICIAL ALA190 PROTEASE (ALA190UPA)              
REMARK 900 RELATED ID: 1GJC   RELATED DB: PDB                                   
REMARK 900 ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OFSER190    
REMARK 900 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS                            
REMARK 900 RELATED ID: 1SC8   RELATED DB: PDB                                   
REMARK 900 UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-J435 COMPLEX                 
REMARK 900 RELATED ID: 1GJA   RELATED DB: PDB                                   
REMARK 900 ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OFSER190    
REMARK 900 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS                            
REMARK 900 RELATED ID: 1O3P   RELATED DB: PDB                                   
REMARK 900 ELABORATE MANIFOLD OF SHORT HYDROGEN BOND ARRAYS MEDIATINGBINDING    
REMARK 900 OF ACTIVE SITE- DIRECTED SERINE PROTEASE INHIBITORS                  
REMARK 900 RELATED ID: 1OWE   RELATED DB: PDB                                   
REMARK 900 SUBSTITUTED 2-NAPHTHAMIDINE INHIBITORS OF UROKINASE                  
REMARK 900 RELATED ID: 1SQA   RELATED DB: PDB                                   
REMARK 900 SUBSTITUTED 2-NAPHTHAMIDINE INHIBITORS OF UROKINASE                  
REMARK 900 RELATED ID: 1GJB   RELATED DB: PDB                                   
REMARK 900 ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OFSER190    
REMARK 900 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS                            
REMARK 900 RELATED ID: 1F92   RELATED DB: PDB                                   
REMARK 900 UROKINASE PLASMINOGEN ACTIVATOR B CHAIN-UKI- 1D COMPLEX              
REMARK 900 RELATED ID: 1OWI   RELATED DB: PDB                                   
REMARK 900 SUBSTITUTED 2-NAPHTHAMIDINE INHIBITORS OF UROKINASE                  
REMARK 900 RELATED ID: 1KDU   RELATED DB: PDB                                   
REMARK 900 PLASMINOGEN ACTIVATOR (UROKINASE-TYPE, KRINGLE DOMAIN) (U-PA K)      
REMARK 900 (NMR, MINIMIZED AVERAGE STRUCTURE)                                   
REMARK 900 RELATED ID: 1SQT   RELATED DB: PDB                                   
REMARK 900 SUBSTITUTED 2-NAPHTHAMIDINE INHIBITORS OF UROKINASE                  
REMARK 900 RELATED ID: 1F5L   RELATED DB: PDB                                   
REMARK 900 UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN- AMILORIDE COMPLEX           
REMARK 900 RELATED ID: 1OWD   RELATED DB: PDB                                   
REMARK 900 SUBSTITUTED 2-NAPHTHAMIDINE INHIBITORS OF UROKINASE                  
REMARK 900 RELATED ID: 1EJN   RELATED DB: PDB                                   
REMARK 900 UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN INHIBITOR COMPLEX            
REMARK 900 RELATED ID: 1LMW   RELATED DB: PDB                                   
REMARK 900 LMW U-PA STRUCTURE COMPLEXED WITH EGRCMK ( GLU-GLY-ARG CHLOROMETHYL  
REMARK 900 KETONE)                                                              
REMARK 900 RELATED ID: 1U6Q   RELATED DB: PDB                                   
REMARK 900 SUBSTITUTED 2-NAPHTHAMADINE INHIBITORS OF UROKINASE                  
REMARK 900 RELATED ID: 1GI8   RELATED DB: PDB                                   
REMARK 900 A NOVEL SERINE PROTEASE INHIBITION MOTIF INVOLVING A MULTI-CENTERED  
REMARK 900 SHORT HYDROGEN BONDING NETWORK AT THE ACTIVE SITE                    
REMARK 900 RELATED ID: 2JDE   RELATED DB: PDB                                   
REMARK 900 UROKINASE-TYPE PLASMINOGEN ACTIVATOR INHIBITOR COMPLEX WITHA 1-(7-   
REMARK 900 SULPHOAMIDOISOQUINOLINYL) GUANIDINE                                  
REMARK 900 RELATED ID: 1C5Y   RELATED DB: PDB                                   
REMARK 900 STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING,    
REMARK 900 SUB- MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR    
REMARK 900 RELATED ID: 1W14   RELATED DB: PDB                                   
REMARK 900 UPA                                                                  
REMARK 900 RELATED ID: 1VJ9   RELATED DB: PDB                                   
REMARK 900 UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-JT464 COMPLEX                
REMARK 900 RELATED ID: 1W13   RELATED DB: PDB                                   
REMARK 900 UPA                                                                  
REMARK 900 RELATED ID: 1GJ7   RELATED DB: PDB                                   
REMARK 900 ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OFSER190    
REMARK 900 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS                            
REMARK 900 RELATED ID: 1C5W   RELATED DB: PDB                                   
REMARK 900 STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING,    
REMARK 900 SUB- MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR    
REMARK 900 RELATED ID: 1OWH   RELATED DB: PDB                                   
REMARK 900 SUBSTITUTED 2-NAPHTHAMIDINE INHIBITORS OF UROKINASE                  
REMARK 900 RELATED ID: 1O5C   RELATED DB: PDB                                   
REMARK 900 DISSECTING AND DESIGNING INHIBITOR SELECTIVITY DETERMINANTSAT THE    
REMARK 900 S1 SITE USING AN ARTIFICIAL ALA190 PROTEASE (ALA190UPA)              
REMARK 900 RELATED ID: 2VIN   RELATED DB: PDB                                   
REMARK 900 FRAGMENT-BASED DISCOVERY OF MEXILETINE DERIVATIVES AS ORALLY         
REMARK 900 BIOAVAILABLE INHIBITORS OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR      
REMARK 900 RELATED ID: 2VIP   RELATED DB: PDB                                   
REMARK 900 FRAGMENT-BASED DISCOVERY OF MEXILETINE DERIVATIVES AS ORALLY         
REMARK 900 BIOAVAILABLE INHIBITORS OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR      
REMARK 900 RELATED ID: 2VIQ   RELATED DB: PDB                                   
REMARK 900 FRAGMENT-BASED DISCOVERY OF MEXILETINE DERIVATIVES AS ORALLY         
REMARK 900 BIOAVAILABLE INHIBITORS OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR      
REMARK 900 RELATED ID: 2VIV   RELATED DB: PDB                                   
REMARK 900 FRAGMENT-BASED DISCOVERY OF MEXILETINE DERIVATIVES AS ORALLY         
REMARK 900 BIOAVAILABLE INHIBITORS OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR      
REMARK 900 RELATED ID: 2VIW   RELATED DB: PDB                                   
REMARK 900 FRAGMENT-BASED DISCOVERY OF MEXILETINE DERIVATIVES AS ORALLY         
REMARK 900 BIOAVAILABLE INHIBITORS OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR      
DBREF  2VIO A   16   250  UNP    P00749   UROK_HUMAN     179    431             
SEQADV 2VIO ILE A   47  UNP  P00749    MET   214 ENGINEERED MUTATION            
SEQADV 2VIO SER A  122  UNP  P00749    CYS   299 ENGINEERED MUTATION            
SEQRES   1 A  253  ILE ILE GLY GLY GLU PHE THR THR ILE GLU ASN GLN PRO          
SEQRES   2 A  253  TRP PHE ALA ALA ILE TYR ARG ARG HIS ARG GLY GLY SER          
SEQRES   3 A  253  VAL THR TYR VAL CYS GLY GLY SER LEU ILE SER PRO CYS          
SEQRES   4 A  253  TRP VAL ILE SER ALA THR HIS CYS PHE ILE ASP TYR PRO          
SEQRES   5 A  253  LYS LYS GLU ASP TYR ILE VAL TYR LEU GLY ARG SER ARG          
SEQRES   6 A  253  LEU ASN SER ASN THR GLN GLY GLU MET LYS PHE GLU VAL          
SEQRES   7 A  253  GLU ASN LEU ILE LEU HIS LYS ASP TYR SER ALA ASP THR          
SEQRES   8 A  253  LEU ALA HIS HIS ASN ASP ILE ALA LEU LEU LYS ILE ARG          
SEQRES   9 A  253  SER LYS GLU GLY ARG CYS ALA GLN PRO SER ARG THR ILE          
SEQRES  10 A  253  GLN THR ILE SER LEU PRO SER MET TYR ASN ASP PRO GLN          
SEQRES  11 A  253  PHE GLY THR SER CYS GLU ILE THR GLY PHE GLY LYS GLU          
SEQRES  12 A  253  ASN SER THR ASP TYR LEU TYR PRO GLU GLN LEU LYS MET          
SEQRES  13 A  253  THR VAL VAL LYS LEU ILE SER HIS ARG GLU CYS GLN GLN          
SEQRES  14 A  253  PRO HIS TYR TYR GLY SER GLU VAL THR THR LYS MET LEU          
SEQRES  15 A  253  CYS ALA ALA ASP PRO GLN TRP LYS THR ASP SER CYS GLN          
SEQRES  16 A  253  GLY ASP SER GLY GLY PRO LEU VAL CYS SER LEU GLN GLY          
SEQRES  17 A  253  ARG MET THR LEU THR GLY ILE VAL SER TRP GLY ARG GLY          
SEQRES  18 A  253  CYS ALA LEU LYS ASP LYS PRO GLY VAL TYR THR ARG VAL          
SEQRES  19 A  253  SER HIS PHE LEU PRO TRP ILE ARG SER HIS THR LYS GLU          
SEQRES  20 A  253  GLU ASN GLY LEU ALA LEU                                      
HET    ACT  A1245       4                                                       
HET    L1O  A1246      15                                                       
HETNAM     ACT ACETATE ION                                                      
HETNAM     L1O 4-(2-AMINOETHOXY)-3,5-DICHLOROBENZOIC ACID                       
FORMUL   2  ACT    C2 H3 O2 1-                                                  
FORMUL   3  L1O    C9 H9 CL2 N O3                                               
FORMUL   4  HOH   *271(H2 O)                                                    
HELIX    1   1 THR A   23  GLN A   27  5                                   5    
HELIX    2   2 ALA A   55  PHE A   59  5                                   5    
HELIX    3   3 LYS A   61  GLU A   62A 5                                   3    
HELIX    4   4 SER A  164  GLN A  169  1                                   6    
HELIX    5   5 TYR A  172  VAL A  176  5                                   5    
HELIX    6   6 PHE A  234  GLU A  244  1                                  11    
SHEET    1  AA 9 GLU A  20  PHE A  21  0                                        
SHEET    2  AA 9 LYS A 156  ILE A 163 -1  O  MET A 157   N  GLU A  20           
SHEET    3  AA 9 MET A 180  ALA A 184 -1  O  CYS A 182   N  ILE A 163           
SHEET    4  AA 9 GLY A 226  ARG A 230 -1  O  GLY A 226   N  ALA A 183           
SHEET    5  AA 9 ARG A 206  TRP A 215 -1  O  ILE A 212   N  THR A 229           
SHEET    6  AA 9 PRO A 198  LEU A 203 -1  O  LEU A 199   N  GLY A 211           
SHEET    7  AA 9 SER A 135  GLY A 140 -1  O  GLU A 137   N  VAL A 200           
SHEET    8  AA 9 LYS A 156  ILE A 163  1  O  LYS A 156   N  GLY A 140           
SHEET    9  AA 9 GLU A  20  PHE A  21 -1  O  GLU A  20   N  MET A 157           
SHEET    1  AB 8 PHE A  30  ARG A  36  0                                        
SHEET    2  AB 8 VAL A  38  SER A  48 -1  O  THR A  39   N  ARG A  35           
SHEET    3  AB 8 TRP A  51  SER A  54 -1  O  TRP A  51   N  ILE A  47           
SHEET    4  AB 8 ALA A 104  ARG A 109 -1  O  ALA A 104   N  SER A  54           
SHEET    5  AB 8 MET A  81  LEU A  90 -1  O  GLU A  84   N  ARG A 109           
SHEET    6  AB 8 TYR A  64  LEU A  68 -1  O  TYR A  64   N  VAL A  85           
SHEET    7  AB 8 PHE A  30  ARG A  36 -1  O  ALA A  32   N  TYR A  67           
SHEET    8  AB 8 PHE A  30  ARG A  36  0                                        
SHEET    1  AC 2 SER A  95  ALA A  96  0                                        
SHEET    2  AC 2 HIS A  99  HIS A 100 -1  O  HIS A 100   N  SER A  95           
SSBOND   1 CYS A   42    CYS A   58                          1555   1555  2.03  
SSBOND   2 CYS A   50    CYS A  111                          1555   1555  2.03  
SSBOND   3 CYS A  136    CYS A  201                          1555   1555  2.02  
SSBOND   4 CYS A  168    CYS A  182                          1555   1555  2.03  
SSBOND   5 CYS A  191    CYS A  220                          1555   1555  2.03  
SITE     1 AC1  5 HIS A  57  GLY A 193  SER A 195  L1O A1246                    
SITE     2 AC1  5 HOH A2267                                                     
SITE     1 AC2 14 HIS A  57  ASP A 189  SER A 190  CYS A 191                    
SITE     2 AC2 14 GLN A 192  SER A 195  VAL A 213  GLY A 216                    
SITE     3 AC2 14 GLY A 219  CYS A 220  ACT A1245  HOH A2269                    
SITE     4 AC2 14 HOH A2270  HOH A2271                                          
CRYST1   52.404   54.184   81.483  90.00  90.00  90.00 P 21 21 21    4          
ORIGX1      1.000000  0.000000  0.000000        0.00000                         
ORIGX2      0.000000  1.000000  0.000000        0.00000                         
ORIGX3      0.000000  0.000000  1.000000        0.00000                         
SCALE1      0.019083  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.018456  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.012272        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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