HEADER HYDROLASE/HYDROLASE INHIBITOR 01-AUG-12 4GE6
TITLE CRYSTAL STRUCTURE OF HUMAN PROTEIN TYROSINE PHOSPHATASE PTPN9 (MEG2)
TITLE 2 COMPLEX WITH COMPOUND 7
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE 9;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: TYROSINE-PROTEIN PHOSPHATASE DOMAIN (UNP RESIDUES 277-582);
COMPND 5 SYNONYM: PROTEIN-TYROSINE PHOSPHATASE MEG2, PTPASE MEG2;
COMPND 6 EC: 3.1.3.48;
COMPND 7 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: PTPN9;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: PHAGE-RESISTANT DERIVATIVE OF BL21(DE3);
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PNIC-CH
KEYWDS HYDROLASE-HYDROLASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR Z.-Y.ZHANG,S.LIU,S.ZHANG
REVDAT 3 13-SEP-23 4GE6 1 REMARK SEQADV
REVDAT 2 14-NOV-12 4GE6 1 JRNL
REVDAT 1 31-OCT-12 4GE6 0
JRNL AUTH S.ZHANG,S.LIU,R.TAO,D.WEI,L.CHEN,W.SHEN,Z.H.YU,L.WANG,
JRNL AUTH 2 D.R.JONES,X.C.DONG,Z.Y.ZHANG
JRNL TITL A HIGHLY SELECTIVE AND POTENT PTP-MEG2 INHIBITOR WITH
JRNL TITL 2 THERAPEUTIC POTENTIAL FOR TYPE 2 DIABETES.
JRNL REF J.AM.CHEM.SOC. V. 134 18116 2012
JRNL REFN ISSN 0002-7863
JRNL PMID 23075115
JRNL DOI 10.1021/JA308212Y
REMARK 2
REMARK 2 RESOLUTION. 1.40 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS 1.1
REMARK 3 AUTHORS : BRUNGER,ADAMS,CLORE,DELANO,GROS,GROSSE-
REMARK 3 : KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,PANNU,
REMARK 3 : READ,RICE,SIMONSON,WARREN
REMARK 3
REMARK 3 REFINEMENT TARGET : ENGH & HUBER
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.40
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 50.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 3637.0
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : NULL
REMARK 3 DATA CUTOFF LOW (ABS(F)) : NULL
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 90.1
REMARK 3 NUMBER OF REFLECTIONS : 100617
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 SET) : 0.198
REMARK 3 FREE R VALUE : 0.215
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 3.600
REMARK 3 FREE R VALUE TEST SET COUNT : 4071
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 (A) : NULL
REMARK 3 BIN RESOLUTION RANGE LOW (A) : NULL
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 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 : 4902
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 64
REMARK 3 SOLVENT ATOMS : 200
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 22.40
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -0.74300
REMARK 3 B22 (A**2) : -1.70300
REMARK 3 B33 (A**2) : 2.44600
REMARK 3 B12 (A**2) : -0.43900
REMARK 3 B13 (A**2) : -0.43400
REMARK 3 B23 (A**2) : -0.44600
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : NULL
REMARK 3 ESD FROM SIGMAA (A) : NULL
REMARK 3 LOW RESOLUTION CUTOFF (A) : NULL
REMARK 3
REMARK 3 CROSS-VALIDATED ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM C-V LUZZATI PLOT (A) : NULL
REMARK 3 ESD FROM C-V SIGMAA (A) : NULL
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.005
REMARK 3 BOND ANGLES (DEGREES) : NULL
REMARK 3 DIHEDRAL ANGLES (DEGREES) : NULL
REMARK 3 IMPROPER ANGLES (DEGREES) : NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : NULL
REMARK 3 KSOL : NULL
REMARK 3 BSOL : 35.02
REMARK 3
REMARK 3 NCS MODEL : NULL
REMARK 3
REMARK 3 NCS RESTRAINTS. RMS SIGMA/WEIGHT
REMARK 3 GROUP 1 POSITIONAL (A) : NULL ; NULL
REMARK 3 GROUP 1 B-FACTOR (A**2) : NULL ; NULL
REMARK 3
REMARK 3 PARAMETER FILE 1 : CNS_TOPPAR:PROTEIN_REP.PARAM
REMARK 3 PARAMETER FILE 2 : CNS_TOPPAR:ION.PARAM
REMARK 3 PARAMETER FILE 3 : B26_PAR.TXT
REMARK 3 PARAMETER FILE 4 : CNS_TOPPAR:WATER.PARAM
REMARK 3 PARAMETER FILE 5 : NULL
REMARK 3 TOPOLOGY FILE 1 : NULL
REMARK 3 TOPOLOGY FILE 2 : NULL
REMARK 3 TOPOLOGY FILE 3 : NULL
REMARK 3 TOPOLOGY FILE 4 : NULL
REMARK 3 TOPOLOGY FILE 5 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4GE6 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 10-AUG-12.
REMARK 100 THE DEPOSITION ID IS D_1000074070.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : NULL
REMARK 200 TEMPERATURE (KELVIN) : NULL
REMARK 200 PH : 6.15
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 19-BM
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : NULL
REMARK 200 MONOCHROMATOR : SI(111)
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 210R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : HKL-3000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 134008
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.240
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 1.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 87.2
REMARK 200 DATA REDUNDANCY : 2.100
REMARK 200 R MERGE (I) : 0.09600
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) : NULL
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : NULL
REMARK 200 COMPLETENESS FOR SHELL (%) : NULL
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : NULL
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : NULL
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: FOURIER SYNTHESIS
REMARK 200 SOFTWARE USED: NULL
REMARK 200 STARTING MODEL: PDB ENTRY 4GE5
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 39.05
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.02
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 25% PEG3350, 0.2 M POTASSIUM
REMARK 280 THIOCYANATE, 10% ETHYLENE GLYCOL, 0.1 M BIS-TRIS PROPANE, PH
REMARK 280 6.15, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,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
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2
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: PISA
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 350
REMARK 350 BIOMOLECULE: 2
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: B
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 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 MET A 276
REMARK 465 SER A 502
REMARK 465 LYS A 503
REMARK 465 GLY A 504
REMARK 465 GLN A 505
REMARK 465 HIS A 584
REMARK 465 HIS A 585
REMARK 465 HIS A 586
REMARK 465 HIS A 587
REMARK 465 HIS A 588
REMARK 465 HIS A 589
REMARK 465 MET B 276
REMARK 465 SER B 502
REMARK 465 LYS B 503
REMARK 465 GLY B 504
REMARK 465 GLN B 505
REMARK 465 HIS B 585
REMARK 465 HIS B 586
REMARK 465 HIS B 587
REMARK 465 HIS B 588
REMARK 465 HIS B 589
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 299 -179.65 67.68
REMARK 500 THR A 347 57.43 -93.97
REMARK 500 LYS A 348 -144.66 -65.21
REMARK 500 HIS A 352 -7.76 -55.84
REMARK 500 THR A 353 83.96 62.71
REMARK 500 GLN A 354 -177.15 -171.14
REMARK 500 ASP A 421 -9.25 78.05
REMARK 500 PRO A 507 -0.03 -54.36
REMARK 500 GLU A 508 114.40 150.51
REMARK 500 ILE A 519 -36.32 -131.88
REMARK 500 ILE A 558 102.57 76.53
REMARK 500 HIS B 284 -8.38 81.71
REMARK 500 GLN B 299 -172.55 61.96
REMARK 500 ASP B 421 -22.76 87.36
REMARK 500 PRO B 507 94.31 -42.00
REMARK 500 GLU B 508 94.78 59.39
REMARK 500 CYS B 515 -124.33 -131.51
REMARK 500 ILE B 558 98.78 74.80
REMARK 500 SER B 582 51.88 -149.83
REMARK 500 ALA B 583 127.20 -15.51
REMARK 500
REMARK 500 REMARK: NULL
REMARK 630
REMARK 630 MOLECULE TYPE: NULL
REMARK 630 MOLECULE NAME: N-(4-BROMO-3-METHYLBENZOYL)-4-[DIFLUORO(PHOSPHONO)
REMARK 630 METHYL]-L-PHENYLALANYL-N~5~-(3-IODOBENZOYL)-L-ORNITHYL-3-{[(4-
REMARK 630 HYDROXY-3-METHOXYPHENYL)ACETYL]AMINO}-D-ALANINAMIDE
REMARK 630 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 630 SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)
REMARK 630
REMARK 630 M RES C SSSEQI
REMARK 630 B26 A 601
REMARK 630 SOURCE: NULL
REMARK 630 TAXONOMY: NULL
REMARK 630 SUBCOMP: 0GF FTY 0G5 0GG NH2
REMARK 630 DETAILS: NULL
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE B26 A 601
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4GE2 RELATED DB: PDB
REMARK 900 RELATED ID: 4GE5 RELATED DB: PDB
DBREF 4GE6 A 277 582 UNP P43378 PTN9_HUMAN 277 582
DBREF 4GE6 B 277 582 UNP P43378 PTN9_HUMAN 277 582
SEQADV 4GE6 MET A 276 UNP P43378 INITIATING METHIONINE
SEQADV 4GE6 ALA A 583 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS A 584 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS A 585 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS A 586 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS A 587 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS A 588 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS A 589 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 MET B 276 UNP P43378 INITIATING METHIONINE
SEQADV 4GE6 ALA B 583 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS B 584 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS B 585 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS B 586 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS B 587 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS B 588 UNP P43378 EXPRESSION TAG
SEQADV 4GE6 HIS B 589 UNP P43378 EXPRESSION TAG
SEQRES 1 A 314 MET SER VAL HIS VAL PRO GLY PRO HIS ALA MET THR ILE
SEQRES 2 A 314 GLN GLU LEU VAL ASP TYR VAL ASN ALA ARG GLN LYS GLN
SEQRES 3 A 314 GLY ILE TYR GLU GLU TYR GLU ASP ILE ARG ARG GLU ASN
SEQRES 4 A 314 PRO VAL GLY THR PHE HIS CYS SER MET SER PRO GLY ASN
SEQRES 5 A 314 LEU GLU LYS ASN ARG TYR GLY ASP VAL PRO CYS LEU ASP
SEQRES 6 A 314 GLN THR ARG VAL LYS LEU THR LYS ARG SER GLY HIS THR
SEQRES 7 A 314 GLN THR ASP TYR ILE ASN ALA SER PHE MET ASP GLY TYR
SEQRES 8 A 314 LYS GLN LYS ASN ALA TYR ILE GLY THR GLN GLY PRO LEU
SEQRES 9 A 314 GLU ASN THR TYR ARG ASP PHE TRP LEU MET VAL TRP GLU
SEQRES 10 A 314 GLN LYS VAL LEU VAL ILE VAL MET THR THR ARG PHE GLU
SEQRES 11 A 314 GLU GLY GLY ARG ARG LYS CYS GLY GLN TYR TRP PRO LEU
SEQRES 12 A 314 GLU LYS ASP SER ARG ILE ARG PHE GLY PHE LEU THR VAL
SEQRES 13 A 314 THR ASN LEU GLY VAL GLU ASN MET ASN HIS TYR LYS LYS
SEQRES 14 A 314 THR THR LEU GLU ILE HIS ASN THR GLU GLU ARG GLN LYS
SEQRES 15 A 314 ARG GLN VAL THR HIS PHE GLN PHE LEU SER TRP PRO ASP
SEQRES 16 A 314 TYR GLY VAL PRO SER SER ALA ALA SER LEU ILE ASP PHE
SEQRES 17 A 314 LEU ARG VAL VAL ARG ASN GLN GLN SER LEU ALA VAL SER
SEQRES 18 A 314 ASN MET GLY ALA ARG SER LYS GLY GLN CYS PRO GLU PRO
SEQRES 19 A 314 PRO ILE VAL VAL HIS CYS SER ALA GLY ILE GLY ARG THR
SEQRES 20 A 314 GLY THR PHE CYS SER LEU ASP ILE CYS LEU ALA GLN LEU
SEQRES 21 A 314 GLU GLU LEU GLY THR LEU ASN VAL PHE GLN THR VAL SER
SEQRES 22 A 314 ARG MET ARG THR GLN ARG ALA PHE SER ILE GLN THR PRO
SEQRES 23 A 314 GLU GLN TYR TYR PHE CYS TYR LYS ALA ILE LEU GLU PHE
SEQRES 24 A 314 ALA GLU LYS GLU GLY MET VAL SER ALA HIS HIS HIS HIS
SEQRES 25 A 314 HIS HIS
SEQRES 1 B 314 MET SER VAL HIS VAL PRO GLY PRO HIS ALA MET THR ILE
SEQRES 2 B 314 GLN GLU LEU VAL ASP TYR VAL ASN ALA ARG GLN LYS GLN
SEQRES 3 B 314 GLY ILE TYR GLU GLU TYR GLU ASP ILE ARG ARG GLU ASN
SEQRES 4 B 314 PRO VAL GLY THR PHE HIS CYS SER MET SER PRO GLY ASN
SEQRES 5 B 314 LEU GLU LYS ASN ARG TYR GLY ASP VAL PRO CYS LEU ASP
SEQRES 6 B 314 GLN THR ARG VAL LYS LEU THR LYS ARG SER GLY HIS THR
SEQRES 7 B 314 GLN THR ASP TYR ILE ASN ALA SER PHE MET ASP GLY TYR
SEQRES 8 B 314 LYS GLN LYS ASN ALA TYR ILE GLY THR GLN GLY PRO LEU
SEQRES 9 B 314 GLU ASN THR TYR ARG ASP PHE TRP LEU MET VAL TRP GLU
SEQRES 10 B 314 GLN LYS VAL LEU VAL ILE VAL MET THR THR ARG PHE GLU
SEQRES 11 B 314 GLU GLY GLY ARG ARG LYS CYS GLY GLN TYR TRP PRO LEU
SEQRES 12 B 314 GLU LYS ASP SER ARG ILE ARG PHE GLY PHE LEU THR VAL
SEQRES 13 B 314 THR ASN LEU GLY VAL GLU ASN MET ASN HIS TYR LYS LYS
SEQRES 14 B 314 THR THR LEU GLU ILE HIS ASN THR GLU GLU ARG GLN LYS
SEQRES 15 B 314 ARG GLN VAL THR HIS PHE GLN PHE LEU SER TRP PRO ASP
SEQRES 16 B 314 TYR GLY VAL PRO SER SER ALA ALA SER LEU ILE ASP PHE
SEQRES 17 B 314 LEU ARG VAL VAL ARG ASN GLN GLN SER LEU ALA VAL SER
SEQRES 18 B 314 ASN MET GLY ALA ARG SER LYS GLY GLN CYS PRO GLU PRO
SEQRES 19 B 314 PRO ILE VAL VAL HIS CYS SER ALA GLY ILE GLY ARG THR
SEQRES 20 B 314 GLY THR PHE CYS SER LEU ASP ILE CYS LEU ALA GLN LEU
SEQRES 21 B 314 GLU GLU LEU GLY THR LEU ASN VAL PHE GLN THR VAL SER
SEQRES 22 B 314 ARG MET ARG THR GLN ARG ALA PHE SER ILE GLN THR PRO
SEQRES 23 B 314 GLU GLN TYR TYR PHE CYS TYR LYS ALA ILE LEU GLU PHE
SEQRES 24 B 314 ALA GLU LYS GLU GLY MET VAL SER ALA HIS HIS HIS HIS
SEQRES 25 B 314 HIS HIS
HET B26 A 601 64
HETNAM B26 N-(4-BROMO-3-METHYLBENZOYL)-4-[DIFLUORO(PHOSPHONO)
HETNAM 2 B26 METHYL]-L-PHENYLALANYL-N~5~-(3-IODOBENZOYL)-L-
HETNAM 3 B26 ORNITHYL-3-{[(4-HYDROXY-3-METHOXYPHENYL)ACETYL]AMINO}-
HETNAM 4 B26 D-ALANINAMIDE
FORMUL 3 B26 C42 H45 BR F2 I N6 O11 P
FORMUL 4 HOH *200(H2 O)
HELIX 1 1 THR A 287 GLU A 313 1 27
HELIX 2 2 PHE A 319 SER A 324 1 6
HELIX 3 3 ASN A 327 ASN A 331 5 5
HELIX 4 4 LEU A 379 ASN A 381 5 3
HELIX 5 5 THR A 382 GLN A 393 1 12
HELIX 6 6 ALA A 477 MET A 498 1 22
HELIX 7 7 ILE A 519 GLY A 539 1 21
HELIX 8 8 ASN A 542 ARG A 551 1 10
HELIX 9 9 THR A 560 GLU A 578 1 19
HELIX 10 10 THR B 287 ALA B 297 1 11
HELIX 11 11 ARG B 298 ARG B 312 1 15
HELIX 12 12 ASN B 327 ASN B 331 5 5
HELIX 13 13 LEU B 339 ARG B 343 5 5
HELIX 14 14 LEU B 379 ASN B 381 5 3
HELIX 15 15 THR B 382 GLN B 393 1 12
HELIX 16 16 ALA B 477 ASN B 497 1 21
HELIX 17 17 GLY B 520 GLY B 539 1 20
HELIX 18 18 ASN B 542 ARG B 551 1 10
HELIX 19 19 THR B 560 GLU B 578 1 19
SHEET 1 A 8 ALA A 360 GLY A 365 0
SHEET 2 A 8 GLN A 368 THR A 375 -1 O GLN A 368 N GLY A 365
SHEET 3 A 8 ILE A 511 HIS A 514 1 O VAL A 513 N ILE A 373
SHEET 4 A 8 VAL A 397 MET A 400 1 N VAL A 399 O VAL A 512
SHEET 5 A 8 GLN A 456 PHE A 465 1 O PHE A 463 N MET A 400
SHEET 6 A 8 TYR A 442 ASN A 451 -1 N ILE A 449 O ARG A 458
SHEET 7 A 8 LEU A 429 ASN A 438 -1 N LEU A 434 O THR A 446
SHEET 8 A 8 ARG A 423 PHE A 426 -1 N PHE A 426 O LEU A 429
SHEET 1 B 2 GLU A 405 GLU A 406 0
SHEET 2 B 2 ARG A 409 ARG A 410 -1 O ARG A 409 N GLU A 406
SHEET 1 C 8 ALA B 360 GLY B 365 0
SHEET 2 C 8 GLN B 368 THR B 375 -1 O GLN B 368 N GLY B 365
SHEET 3 C 8 ILE B 511 HIS B 514 1 O VAL B 513 N ILE B 373
SHEET 4 C 8 VAL B 397 MET B 400 1 N VAL B 399 O VAL B 512
SHEET 5 C 8 GLN B 456 PHE B 465 1 O PHE B 463 N MET B 400
SHEET 6 C 8 TYR B 442 ASN B 451 -1 N LEU B 447 O VAL B 460
SHEET 7 C 8 LEU B 429 ASN B 438 -1 N LEU B 434 O THR B 446
SHEET 8 C 8 ARG B 423 PHE B 426 -1 N PHE B 426 O LEU B 429
SHEET 1 D 2 GLU B 405 GLU B 406 0
SHEET 2 D 2 ARG B 409 ARG B 410 -1 O ARG B 409 N GLU B 406
CISPEP 1 GLY A 282 PRO A 283 0 0.02
CISPEP 2 GLY B 282 PRO B 283 0 -0.17
SITE 1 AC1 17 GLU A 308 ARG A 311 TYR A 333 ASP A 335
SITE 2 AC1 17 SER A 496 CYS A 506 PRO A 507 CYS A 515
SITE 3 AC1 17 SER A 516 ALA A 517 ILE A 519 GLY A 520
SITE 4 AC1 17 ARG A 521 PHE A 556 GLN A 559 PRO A 561
SITE 5 AC1 17 HIS B 584
CRYST1 40.137 57.774 66.702 77.22 78.03 80.01 P 1 2
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 0.024915 -0.004389 -0.004523 0.00000
SCALE2 0.000000 0.017575 -0.003443 0.00000
SCALE3 0.000000 0.000000 0.015617 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
