HEADER TRANSFERASE 04-NOV-04 1WBN
TITLE FRAGMENT BASED P38 INHIBITORS
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: MITOGEN-ACTIVATED PROTEIN KINASE 14;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: MITOGEN-ACTIVATED PROTEIN KINASE P38ALPHA, MAP
COMPND 5 KINASE P38ALPHA, CYTOKINE SUPPRESSIVE ANTI-INFLAMMATORY
COMPND 6 DRUG BINDING PROTEIN, CSAID BINDING PROTEIN, CSBP,
COMPND 7 MAX-INTERACTING PROTEIN 2, MAP KINASE MXI2, SAPK2A;
COMPND 8 EC: 2.7.1.37;
COMPND 9 ENGINEERED: 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: 469008;
SOURCE 7 EXPRESSION_SYSTEM_STRAIN: BL21(DE3)
KEYWDS P38 MAP KINASE, INHIBITOR STRUCTURE, ALTERNATIVE SPLICING,
KEYWDS 2 ATP-BINDING, NUCLEAR PROTEIN, PHOSPHORYLATION,
KEYWDS 3 SERINE/THREONINE PROTEIN KINASE, TRANSFERASE
EXPDTA X-RAY DIFFRACTION
AUTHOR A.CLEASBY,L.A.DEVINE,A.L.GILL,H.JHOTI
REVDAT 2 24-FEB-09 1WBN 1 VERSN
REVDAT 1 03-NOV-05 1WBN 0
JRNL AUTH A.L.GILL,M.FREDERICKSON,A.CLEASBY,S.J.WOODHEAD,
JRNL AUTH 2 M.G.CARR,A.J.WOODHEAD,M.T.WALKER,M.S.CONGREVE,
JRNL AUTH 3 L.A.DEVINE,D.TISI,M.O'REILLY,L.C.SEAVERS,D.J.DAVIS,
JRNL AUTH 4 J.CURRY,R.ANTHONY,A.PADOVA,C.W.MURRAY,R.A.CARR,
JRNL AUTH 5 H.JHOTI
JRNL TITL IDENTIFICATION OF NOVEL P38ALPHA MAP KINASE
JRNL TITL 2 INHIBITORS USING FRAGMENT-BASED LEAD GENERATION.
JRNL REF J.MED.CHEM. V. 48 414 2005
JRNL REFN ISSN 0022-2623
JRNL PMID 15658855
JRNL DOI 10.1021/JM049575N
REMARK 2
REMARK 2 RESOLUTION. 2.4 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS
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 : NULL
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.40
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 43.316
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.0
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : 10000
REMARK 3 DATA CUTOFF LOW (ABS(F)) : NULL
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 94.8
REMARK 3 NUMBER OF REFLECTIONS : 19221
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) : 0.1808
REMARK 3 FREE R VALUE : 0.2438
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 4.9
REMARK 3 FREE R VALUE TEST SET COUNT : 994
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 : 2834
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 28
REMARK 3 SOLVENT ATOMS : 552
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) : -0.133
REMARK 3 B22 (A**2) : 0.642
REMARK 3 B33 (A**2) : -0.509
REMARK 3 B12 (A**2) : 0.000
REMARK 3 B13 (A**2) : 0.000
REMARK 3 B23 (A**2) : 0.000
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) : 0.005089
REMARK 3 BOND ANGLES (DEGREES) : 0.84608
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 : 0.362674
REMARK 3 BSOL : 38.9062
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 : PROTEIN_REP.PARAM
REMARK 3 PARAMETER FILE 2 : WATER_REP.PARAM
REMARK 3 PARAMETER FILE 3 : ION.PARAM
REMARK 3 PARAMETER FILE 4 : LIGANDS.PAR
REMARK 3 PARAMETER FILE 5 : NULL
REMARK 3 TOPOLOGY FILE 1 : PROTEIN.TOP
REMARK 3 TOPOLOGY FILE 2 : WATER.TOP
REMARK 3 TOPOLOGY FILE 3 : ION.TOP
REMARK 3 TOPOLOGY FILE 4 : LIGANDS.TOP
REMARK 3 TOPOLOGY FILE 5 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 1WBN COMPLIES WITH FORMAT V. 3.15, 01-DEC-08
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 04-NOV-04.
REMARK 100 THE PDBE ID CODE IS EBI-21532.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : NULL
REMARK 200 TEMPERATURE (KELVIN) : 100.0
REMARK 200 PH : 7.00
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SRS
REMARK 200 BEAMLINE : PX14.1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.933
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : CCP4 (SCALA)
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 19222
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.400
REMARK 200 RESOLUTION RANGE LOW (A) : 43.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 96.2
REMARK 200 DATA REDUNDANCY : 3.400
REMARK 200 R MERGE (I) : 0.08000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 6.7000
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: OTHER
REMARK 200 SOFTWARE USED: NULL
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 56
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA):NULL
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: NULL
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 23.07050
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 62.86450
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 43.00050
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 62.86450
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 23.07050
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 43.00050
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 GENERATING THE BIOMOLECULE
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 FUNCTION: RESPONDS TO ACTIVATION BY ENVIRONMENTAL STRESS, PRO-
REMARK 400 INFLAMMATORY CYTOKINES AND LIPOPOLYSACCHARIDE (LPS) BY
REMARK 400 PHOSPHORYLATING A NUMBER OF TRANSCRIPTION FACTORS, SUCH AS ELK1
REMARK 400 AND ATF2 AND SEVERAL DOWNSTREAM KINASES, SUCH AS MAPKAPK2 AND
REMARK 400 MAPKAPK5. PLAYS A CRITICAL ROLE IN THE PRODUCTION OF SOME
REMARK 400 CYTOKINES, FOR EXAMPLE IL-6. ISOFORM MXI2 ACTIVATION IS
REMARK 400 STIMULATED BY MITOGENS AND OXIDATIVE STRESS AND ONLY POORLY
REMARK 400 PHOSPHORYLATES ELK1 AND ATF2.
REMARK 400 CATALYTIC ACTIVITY: ATP + A PROTEIN = ADP + A PHOSPHOPROTEIN.
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 1
REMARK 465 SER A 2
REMARK 465 GLN A 3
REMARK 465 GLU A 356
REMARK 465 GLU A 357
REMARK 465 MET A 358
REMARK 465 GLU A 359
REMARK 465 SER A 360
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 GLN A 355 CA C O CB CG CD OE1 NE2
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 2113 - O HOH A 2295 2.16
REMARK 500 O HOH A 2280 - O HOH A 2304 2.08
REMARK 500 O HOH A 2285 - O HOH A 2502 2.15
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 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 ARG A 57 74.91 30.87
REMARK 500 ARG A 149 -15.66 78.68
REMARK 500
REMARK 500 REMARK: NULL
REMARK 525
REMARK 525 SOLVENT
REMARK 525
REMARK 525 THE SOLVENT MOLECULES HAVE CHAIN IDENTIFIERS THAT
REMARK 525 INDICATE THE POLYMER CHAIN WITH WHICH THEY ARE MOST
REMARK 525 CLOSELY ASSOCIATED. THE REMARK LISTS ALL THE SOLVENT
REMARK 525 MOLECULES WHICH ARE MORE THAN 5A AWAY FROM THE
REMARK 525 NEAREST POLYMER CHAIN (M = MODEL NUMBER;
REMARK 525 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE
REMARK 525 NUMBER; I=INSERTION CODE):
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE L09 A1355
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 1A9U RELATED DB: PDB
REMARK 900 THE COMPLEX STRUCTURE OF THE MAP KINASE
REMARK 900 P38/SB203580
REMARK 900 RELATED ID: 1BL6 RELATED DB: PDB
REMARK 900 THE COMPLEX STRUCTURE OF THE MAP KINASE
REMARK 900 P38/SB216995
REMARK 900 RELATED ID: 1BL7 RELATED DB: PDB
REMARK 900 THE COMPLEX STRUCTURE OF THE MAP KINASE
REMARK 900 P38/SB220025
REMARK 900 RELATED ID: 1BMK RELATED DB: PDB
REMARK 900 THE COMPLEX STRUCTURE OF THE MAP KINASE
REMARK 900 P38/SB218655
REMARK 900 RELATED ID: 1DI9 RELATED DB: PDB
REMARK 900 THE STRUCTURE OF P38 MITOGEN-ACTIVATED
REMARK 900 PROTEIN KINASE INCOMPLEX WITH 4-[3-
REMARK 900 METHYLSULFANYLANILINO]-6,7-DIMETHOXYQUINAZOLINE
REMARK 900 RELATED ID: 1IAN RELATED DB: PDB
REMARK 900 HUMAN P38 MAP KINASE INHIBITOR COMPLEX
REMARK 900 RELATED ID: 1KV1 RELATED DB: PDB
REMARK 900 P38 MAP KINASE IN COMPLEX WITH INHIBITOR 1
REMARK 900 RELATED ID: 1KV2 RELATED DB: PDB
REMARK 900 HUMAN P38 MAP KINASE IN COMPLEX WITH BIRB
REMARK 900 796
REMARK 900 RELATED ID: 1M7Q RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF P38 MAP KINASE IN
REMARK 900 COMPLEX WITH ADIHYDROQUINAZOLINONE INHIBITOR
REMARK 900 RELATED ID: 1OUK RELATED DB: PDB
REMARK 900 THE STRUCTURE OF P38 ALPHA IN COMPLEX WITH
REMARK 900 APYRIDINYLIMIDAZOLE INHIBITOR
REMARK 900 RELATED ID: 1OUY RELATED DB: PDB
REMARK 900 THE STRUCTURE OF P38 ALPHA IN COMPLEX WITH
REMARK 900 A DIHYDROPYRIDO-PYRIMIDINE INHIBITOR
REMARK 900 RELATED ID: 1OVE RELATED DB: PDB
REMARK 900 THE STRUCTURE OF P38 ALPHA IN COMPLEX WITH
REMARK 900 ADIHYDROQUINOLINONE
REMARK 900 RELATED ID: 1OZ1 RELATED DB: PDB
REMARK 900 P38 MITOGEN-ACTIVATED KINASE IN COMPLEX WITH
REMARK 900 4-AZAINDOLEINHIBITOR
REMARK 900 RELATED ID: 1R39 RELATED DB: PDB
REMARK 900 THE STRUCTURE OF P38ALPHA
REMARK 900 RELATED ID: 1R3C RELATED DB: PDB
REMARK 900 THE STRUCTURE OF P38ALPHA C162S MUTANT
REMARK 900 RELATED ID: 1W7H RELATED DB: PDB
REMARK 900 P38 KINASE CRYSTAL STRUCTURE IN COMPLEX WITH
REMARK 900 SMALL MOLECULE INHIBITOR
REMARK 900 RELATED ID: 1W82 RELATED DB: PDB
REMARK 900 P38 KINASE CRYSTAL STRUCTURE IN COMPLEX WITH
REMARK 900 SMALL MOLECULE INHIBITOR
REMARK 900 RELATED ID: 1W83 RELATED DB: PDB
REMARK 900 P38 KINASE CRYSTAL STRUCTURE IN COMPLEX WITH
REMARK 900 SMALL MOLECULE INHIBITOR
REMARK 900 RELATED ID: 1W84 RELATED DB: PDB
REMARK 900 P38 KINASE CRYSTAL STRUCTURE IN COMPLEX WITH
REMARK 900 SMALL MOLECULE INHIBITOR
REMARK 900 RELATED ID: 1WBO RELATED DB: PDB
REMARK 900 FRAGMENT BASED P38 INHIBITORS
REMARK 900 RELATED ID: 1WBS RELATED DB: PDB
REMARK 900 IDENTIFICATION OF NOVEL P38 ALPHA MAP KINASE
REMARK 900 INHIBITORS USING FRAGMENT-BASED LEAD
REMARK 900 GENERATION.
REMARK 900 RELATED ID: 1WBT RELATED DB: PDB
REMARK 900 IDENTIFICATION OF NOVEL P38 ALPHA MAP KINASE
REMARK 900 INHIBITORS USING FRAGMENT-BASED LEAD
REMARK 900 GENERATION.
REMARK 900 RELATED ID: 1WBV RELATED DB: PDB
REMARK 900 IDENTIFICATION OF NOVEL P38 ALPHA MAP KINASE
REMARK 900 INHIBITORS USING FRAGMENT-BASED LEAD
REMARK 900 GENERATION.
REMARK 900 RELATED ID: 1WBW RELATED DB: PDB
REMARK 900 IDENTIFICATION OF NOVEL P38 ALPHA MAP KINASE
REMARK 900 INHIBITORS USING FRAGMENT-BASED LEAD
REMARK 900 GENERATION.
REMARK 900 RELATED ID: 1WFC RELATED DB: PDB
REMARK 900 STRUCTURE OF APO, UNPHOSPHORYLATED, P38
REMARK 900 MITOGEN ACTIVATEDPROTEIN KINASE P38 (P38 MAP
REMARK 900 KINASE) THE MAMMALIAN HOMOLOGUEOF THE YEAST
REMARK 900 HOG1 PROTEIN
REMARK 900 RELATED ID: 1YQJ RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF P38 ALPHA IN COMPLEX
REMARK 900 WITH A SELECTIVEPYRIDAZINE INHIBITOR
REMARK 900 RELATED ID: 1ZZ2 RELATED DB: PDB
REMARK 900 TWO CLASSES OF P38ALPHA MAP KINASE
REMARK 900 INHIBITORS HAVING ACOMMON DIPHENYLETHER CORE
REMARK 900 BUT EXHIBITING DIVERGENT BINDINGMODES
REMARK 900 RELATED ID: 1ZZL RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF P38 WITH TRIAZOLOPYRIDINE
REMARK 999
REMARK 999 SEQUENCE
REMARK 999 THE INITIAL MET WAS NOT OBSERVED IN THE SEQUENCING
REMARK 999 EXPERIMENT THAT DETERMINED THE SEQUENCE OF THE UNIPROT
REMARK 999 ENTRY, BUT THIS INITIAL MET IS PRESUMED TO EXIST AND
REMARK 999 IS DESCRIBED IN AN ANNOTATION IN THE UNIPROT ENTRY.
DBREF 1WBN A 1 1 PDB 1WBN 1WBN 1 1
DBREF 1WBN A 2 360 UNP Q16539 MK14_HUMAN 1 359
SEQRES 1 A 360 MET SER GLN GLU ARG PRO THR PHE TYR ARG GLN GLU LEU
SEQRES 2 A 360 ASN LYS THR ILE TRP GLU VAL PRO GLU ARG TYR GLN ASN
SEQRES 3 A 360 LEU SER PRO VAL GLY SER GLY ALA TYR GLY SER VAL CYS
SEQRES 4 A 360 ALA ALA PHE ASP THR LYS THR GLY LEU ARG VAL ALA VAL
SEQRES 5 A 360 LYS LYS LEU SER ARG PRO PHE GLN SER ILE ILE HIS ALA
SEQRES 6 A 360 LYS ARG THR TYR ARG GLU LEU ARG LEU LEU LYS HIS MET
SEQRES 7 A 360 LYS HIS GLU ASN VAL ILE GLY LEU LEU ASP VAL PHE THR
SEQRES 8 A 360 PRO ALA ARG SER LEU GLU GLU PHE ASN ASP VAL TYR LEU
SEQRES 9 A 360 VAL THR HIS LEU MET GLY ALA ASP LEU ASN ASN ILE VAL
SEQRES 10 A 360 LYS CYS GLN LYS LEU THR ASP ASP HIS VAL GLN PHE LEU
SEQRES 11 A 360 ILE TYR GLN ILE LEU ARG GLY LEU LYS TYR ILE HIS SER
SEQRES 12 A 360 ALA ASP ILE ILE HIS ARG ASP LEU LYS PRO SER ASN LEU
SEQRES 13 A 360 ALA VAL ASN GLU ASP CYS GLU LEU LYS ILE LEU ASP PHE
SEQRES 14 A 360 GLY LEU ALA ARG HIS THR ASP ASP GLU MET THR GLY TYR
SEQRES 15 A 360 VAL ALA THR ARG TRP TYR ARG ALA PRO GLU ILE MET LEU
SEQRES 16 A 360 ASN TRP MET HIS TYR ASN GLN THR VAL ASP ILE TRP SER
SEQRES 17 A 360 VAL GLY CYS ILE MET ALA GLU LEU LEU THR GLY ARG THR
SEQRES 18 A 360 LEU PHE PRO GLY THR ASP HIS ILE ASP GLN LEU LYS LEU
SEQRES 19 A 360 ILE LEU ARG LEU VAL GLY THR PRO GLY ALA GLU LEU LEU
SEQRES 20 A 360 LYS LYS ILE SER SER GLU SER ALA ARG ASN TYR ILE GLN
SEQRES 21 A 360 SER LEU THR GLN MET PRO LYS MET ASN PHE ALA ASN VAL
SEQRES 22 A 360 PHE ILE GLY ALA ASN PRO LEU ALA VAL ASP LEU LEU GLU
SEQRES 23 A 360 LYS MET LEU VAL LEU ASP SER ASP LYS ARG ILE THR ALA
SEQRES 24 A 360 ALA GLN ALA LEU ALA HIS ALA TYR PHE ALA GLN TYR HIS
SEQRES 25 A 360 ASP PRO ASP ASP GLU PRO VAL ALA ASP PRO TYR ASP GLN
SEQRES 26 A 360 SER PHE GLU SER ARG ASP LEU LEU ILE ASP GLU TRP LYS
SEQRES 27 A 360 SER LEU THR TYR ASP GLU VAL ILE SER PHE VAL PRO PRO
SEQRES 28 A 360 PRO LEU ASP GLN GLU GLU MET GLU SER
HET L09 A1355 28
HETNAM L09 N-(3-TERT-BUTYL-1H-PYRAZOL-5-YL)-N'-{4-
HETNAM 2 L09 CHLORO-3-[(PYRIDIN-3-YLOXY)METHYL]PHENYL}
HETNAM 3 L09 UREA
HETSYN L09 P38 MAP KINASE INHIBITOR
FORMUL 2 L09 C20 H22 CL N5 O2
FORMUL 3 HOH *552(H2 O1)
HELIX 1 1 SER A 61 MET A 78 1 18
HELIX 2 2 SER A 95 PHE A 99 5 5
HELIX 3 3 ASP A 112 GLN A 120 1 9
HELIX 4 4 THR A 123 ALA A 144 1 22
HELIX 5 5 LYS A 152 SER A 154 5 3
HELIX 6 6 VAL A 183 TYR A 188 1 6
HELIX 7 7 ALA A 190 LEU A 195 1 6
HELIX 8 8 GLN A 202 GLY A 219 1 18
HELIX 9 9 ASP A 227 GLY A 240 1 14
HELIX 10 10 GLY A 243 LYS A 249 1 7
HELIX 11 11 SER A 252 GLN A 260 1 9
HELIX 12 12 ASN A 269 VAL A 273 5 5
HELIX 13 13 ASN A 278 LEU A 289 1 12
HELIX 14 14 ASP A 292 ARG A 296 5 5
HELIX 15 15 THR A 298 ALA A 304 1 7
HELIX 16 16 HIS A 305 ALA A 309 5 5
HELIX 17 17 GLN A 325 ARG A 330 5 6
HELIX 18 18 LEU A 333 PHE A 348 1 16
SHEET 1 AA 2 PHE A 8 GLU A 12 0
SHEET 2 AA 2 ILE A 17 PRO A 21 -1 O TRP A 18 N GLN A 11
SHEET 1 AB 5 TYR A 24 GLY A 33 0
SHEET 2 AB 5 GLY A 36 ASP A 43 -1 O GLY A 36 N GLY A 33
SHEET 3 AB 5 LEU A 48 LEU A 55 -1 O LEU A 48 N ASP A 43
SHEET 4 AB 5 TYR A 103 HIS A 107 -1 O LEU A 104 N LYS A 53
SHEET 5 AB 5 ASP A 88 PHE A 90 -1 O ASP A 88 N VAL A 105
SHEET 1 AC 2 LEU A 156 VAL A 158 0
SHEET 2 AC 2 LEU A 164 ILE A 166 -1 O LYS A 165 N ALA A 157
SITE 1 AC1 15 ALA A 51 LYS A 53 GLU A 71 LEU A 74
SITE 2 AC1 15 LEU A 75 MET A 78 ILE A 84 THR A 106
SITE 3 AC1 15 MET A 109 ILE A 166 LEU A 167 ASP A 168
SITE 4 AC1 15 HOH A2550 HOH A2551 HOH A2552
CRYST1 46.141 86.001 125.729 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 0.021673 0.000000 0.000000 0.00000
SCALE2 0.000000 0.011628 0.000000 0.00000
SCALE3 0.000000 0.000000 0.007954 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
