HEADER SIGNALING PROTEIN 10-APR-18 6G92
TITLE FRAGMENT-BASED DISCOVERY OF A HIGHLY POTENT, ORALLY BIOAVAILABLE
TITLE 2 INHIBITOR WHICH MODULATES THE PHOSPHORYLATION AND CATALYTIC ACTIVITY
TITLE 3 OF ERK1/2
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: MITOGEN-ACTIVATED PROTEIN KINASE 1;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: MAPK 1,ERT1,EXTRACELLULAR SIGNAL-REGULATED KINASE 2,ERK-2,
COMPND 5 MAP KINASE ISOFORM P42,P42-MAPK,MITOGEN-ACTIVATED PROTEIN KINASE 2,
COMPND 6 MAPK 2;
COMPND 7 EC: 2.7.11.24;
COMPND 8 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: MAPK1, ERK2, PRKM1, PRKM2;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 511693
KEYWDS ERK2 KINASE INHIBITOR, SIGNALING PROTEIN
EXPDTA X-RAY DIFFRACTION
AUTHOR M.O'REILLY
REVDAT 3 27-JUN-18 6G92 1 JRNL
REVDAT 2 13-JUN-18 6G92 1 JRNL
REVDAT 1 30-MAY-18 6G92 0
JRNL AUTH T.D.HEIGHTMAN,V.BERDINI,H.BRAITHWAITE,I.M.BUCK,M.CASSIDY,
JRNL AUTH 2 J.CASTRO,A.COURTIN,J.E.H.DAY,C.EAST,L.FAZAL,B.GRAHAM,
JRNL AUTH 3 C.M.GRIFFITHS-JONES,J.F.LYONS,V.MARTINS,S.MUENCH,J.M.MUNCK,
JRNL AUTH 4 D.NORTON,M.O'REILLY,N.PALMER,P.PATHURI,M.READER,D.C.REES,
JRNL AUTH 5 S.J.RICH,C.RICHARDSON,H.SAINI,N.T.THOMPSON,N.G.WALLIS,
JRNL AUTH 6 H.WALTON,N.E.WILSHER,A.J.WOOLFORD,M.COOKE,D.COUSIN,S.ONIONS,
JRNL AUTH 7 J.SHANNON,J.WATTS,C.W.MURRAY
JRNL TITL FRAGMENT-BASED DISCOVERY OF A POTENT, ORALLY BIOAVAILABLE
JRNL TITL 2 INHIBITOR THAT MODULATES THE PHOSPHORYLATION AND CATALYTIC
JRNL TITL 3 ACTIVITY OF ERK1/2.
JRNL REF J. MED. CHEM. V. 61 4978 2018
JRNL REFN ISSN 1520-4804
JRNL PMID 29775310
JRNL DOI 10.1021/ACS.JMEDCHEM.8B00421
REMARK 2
REMARK 2 RESOLUTION. 1.99 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER 2.11.7
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SHARFF,SMART,VONRHEIN,
REMARK 3 : WOMACK,MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.99
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 30.12
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.4
REMARK 3 NUMBER OF REFLECTIONS : 26572
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) : 0.167
REMARK 3 R VALUE (WORKING SET) : 0.164
REMARK 3 FREE R VALUE : 0.227
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.250
REMARK 3 FREE R VALUE TEST SET COUNT : 1394
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 : 13
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 1.99
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.07
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 96.29
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2916
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.2140
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2765
REMARK 3 BIN R VALUE (WORKING SET) : 0.2106
REMARK 3 BIN FREE R VALUE : 0.2797
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.18
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 151
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 : 2798
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 30
REMARK 3 SOLVENT ATOMS : 522
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 23.59
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 33.17
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 2.35550
REMARK 3 B22 (A**2) : -3.27580
REMARK 3 B33 (A**2) : 0.92030
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 2.24700
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.200
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : 0.192
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.170
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.434
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : 0.160
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 : 0.947
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.916
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 5719 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 10348 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 1258 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 74 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 842 ; 16.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 5713 ; 20.000 ; HARMONIC
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 : 371 ; 5.000 ; SEMIHARMONIC
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 : 6659 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.012
REMARK 3 BOND ANGLES (DEGREES) : 1.08
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 5.94
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 16.12
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 1
REMARK 3
REMARK 3 TLS GROUP : 1
REMARK 3 SELECTION: { A|8 - A|365 }
REMARK 3 ORIGIN FOR THE GROUP (A): -0.7498 3.6625 38.0872
REMARK 3 T TENSOR
REMARK 3 T11: -0.0518 T22: -0.0530
REMARK 3 T33: -0.0498 T12: 0.0100
REMARK 3 T13: -0.0002 T23: -0.0330
REMARK 3 L TENSOR
REMARK 3 L11: 1.1309 L22: 0.4494
REMARK 3 L33: 0.8341 L12: -0.2748
REMARK 3 L13: 0.3998 L23: -0.1645
REMARK 3 S TENSOR
REMARK 3 S11: -0.0827 S12: -0.1524 S13: 0.1196
REMARK 3 S21: 0.0924 S22: 0.0505 S23: -0.0371
REMARK 3 S31: -0.0555 S32: -0.0651 S33: 0.0322
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 6G92 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 11-APR-18.
REMARK 100 THE DEPOSITION ID IS D_1200009600.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 13-NOV-14
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.2
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 FR-E SUPERBRIGHT
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.54178
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : RIGAKU SATURN 944
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : AIMLESS
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 26685
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.990
REMARK 200 RESOLUTION RANGE LOW (A) : 46.140
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.4
REMARK 200 DATA REDUNDANCY : 3.300
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 5.8000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.99
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.03
REMARK 200 COMPLETENESS FOR SHELL (%) : 95.5
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.85000
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: BUSTER
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 46.91
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.32
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.2M (NH4)2SO4, 0.1M HEPES/NAOHPH=7.2,
REMARK 280 34.0%W/V MPEG 2000, 0.02M MERCAPTOETHANOL, PH 7.2, VAPOR
REMARK 280 DIFFUSION, SITTING DROP, TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 1 21 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,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 0.00000
REMARK 290 SMTRY2 2 0.000000 1.000000 0.000000 35.50550
REMARK 290 SMTRY3 2 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: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 440 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 16820 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -27.0 KCAL/MOL
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 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 -7
REMARK 465 ALA A -6
REMARK 465 HIS A -5
REMARK 465 HIS A -4
REMARK 465 HIS A -3
REMARK 465 HIS A -2
REMARK 465 HIS A -1
REMARK 465 HIS A 0
REMARK 465 MET A 1
REMARK 465 ALA A 2
REMARK 465 ALA A 3
REMARK 465 ALA A 4
REMARK 465 ALA A 5
REMARK 465 ALA A 6
REMARK 465 ALA A 7
REMARK 465 LYS A 330
REMARK 465 PHE A 331
REMARK 465 ASP A 332
REMARK 465 MET A 333
REMARK 465 GLU A 334
REMARK 465 LEU A 335
REMARK 465 TYR A 358
REMARK 465 ARG A 359
REMARK 465 SER A 360
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 ILE A 31 -60.64 -107.92
REMARK 500 ASP A 149 46.50 -151.84
REMARK 500 ASP A 167 83.92 66.15
REMARK 500 ASN A 201 18.14 -158.44
REMARK 500 LEU A 294 53.57 -95.91
REMARK 500 LEU A 294 53.57 -96.51
REMARK 500 ASP A 318 89.83 -162.17
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 525
REMARK 525 M RES CSSEQI
REMARK 525 HOH A1018 DISTANCE = 5.82 ANGSTROMS
REMARK 525 HOH A1019 DISTANCE = 6.03 ANGSTROMS
REMARK 525 HOH A1020 DISTANCE = 6.08 ANGSTROMS
REMARK 525 HOH A1021 DISTANCE = 6.33 ANGSTROMS
REMARK 525 HOH A1022 DISTANCE = 7.77 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 402
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 403
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue ERZ A 404
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 6G8X RELATED DB: PDB
REMARK 900 RELATED ID: 6G9I RELATED DB: PDB
DBREF 6G92 A 1 360 UNP P28482 MK01_HUMAN 1 360
SEQADV 6G92 MET A -7 UNP P28482 INITIATING METHIONINE
SEQADV 6G92 ALA A -6 UNP P28482 EXPRESSION TAG
SEQADV 6G92 HIS A -5 UNP P28482 EXPRESSION TAG
SEQADV 6G92 HIS A -4 UNP P28482 EXPRESSION TAG
SEQADV 6G92 HIS A -3 UNP P28482 EXPRESSION TAG
SEQADV 6G92 HIS A -2 UNP P28482 EXPRESSION TAG
SEQADV 6G92 HIS A -1 UNP P28482 EXPRESSION TAG
SEQADV 6G92 HIS A 0 UNP P28482 EXPRESSION TAG
SEQRES 1 A 368 MET ALA HIS HIS HIS HIS HIS HIS MET ALA ALA ALA ALA
SEQRES 2 A 368 ALA ALA GLY ALA GLY PRO GLU MET VAL ARG GLY GLN VAL
SEQRES 3 A 368 PHE ASP VAL GLY PRO ARG TYR THR ASN LEU SER TYR ILE
SEQRES 4 A 368 GLY GLU GLY ALA TYR GLY MET VAL CYS SER ALA TYR ASP
SEQRES 5 A 368 ASN VAL ASN LYS VAL ARG VAL ALA ILE LYS LYS ILE SER
SEQRES 6 A 368 PRO PHE GLU HIS GLN THR TYR CYS GLN ARG THR LEU ARG
SEQRES 7 A 368 GLU ILE LYS ILE LEU LEU ARG PHE ARG HIS GLU ASN ILE
SEQRES 8 A 368 ILE GLY ILE ASN ASP ILE ILE ARG ALA PRO THR ILE GLU
SEQRES 9 A 368 GLN MET LYS ASP VAL TYR ILE VAL GLN ASP LEU MET GLU
SEQRES 10 A 368 THR ASP LEU TYR LYS LEU LEU LYS THR GLN HIS LEU SER
SEQRES 11 A 368 ASN ASP HIS ILE CYS TYR PHE LEU TYR GLN ILE LEU ARG
SEQRES 12 A 368 GLY LEU LYS TYR ILE HIS SER ALA ASN VAL LEU HIS ARG
SEQRES 13 A 368 ASP LEU LYS PRO SER ASN LEU LEU LEU ASN THR THR CME
SEQRES 14 A 368 ASP LEU LYS ILE CYS ASP PHE GLY LEU ALA ARG VAL ALA
SEQRES 15 A 368 ASP PRO ASP HIS ASP HIS THR GLY PHE LEU THR GLU TYR
SEQRES 16 A 368 VAL ALA THR ARG TRP TYR ARG ALA PRO GLU ILE MET LEU
SEQRES 17 A 368 ASN SER LYS GLY TYR THR LYS SER ILE ASP ILE TRP SER
SEQRES 18 A 368 VAL GLY CYS ILE LEU ALA GLU MET LEU SER ASN ARG PRO
SEQRES 19 A 368 ILE PHE PRO GLY LYS HIS TYR LEU ASP GLN LEU ASN HIS
SEQRES 20 A 368 ILE LEU GLY ILE LEU GLY SER PRO SER GLN GLU ASP LEU
SEQRES 21 A 368 ASN CYS ILE ILE ASN LEU LYS ALA ARG ASN TYR LEU LEU
SEQRES 22 A 368 SER LEU PRO HIS LYS ASN LYS VAL PRO TRP ASN ARG LEU
SEQRES 23 A 368 PHE PRO ASN ALA ASP SER LYS ALA LEU ASP LEU LEU ASP
SEQRES 24 A 368 LYS MET LEU THR PHE ASN PRO HIS LYS ARG ILE GLU VAL
SEQRES 25 A 368 GLU GLN ALA LEU ALA HIS PRO TYR LEU GLU GLN TYR TYR
SEQRES 26 A 368 ASP PRO SER ASP GLU PRO ILE ALA GLU ALA PRO PHE LYS
SEQRES 27 A 368 PHE ASP MET GLU LEU ASP ASP LEU PRO LYS GLU LYS LEU
SEQRES 28 A 368 LYS GLU LEU ILE PHE GLU GLU THR ALA ARG PHE GLN PRO
SEQRES 29 A 368 GLY TYR ARG SER
MODRES 6G92 CME A 161 CYS MODIFIED RESIDUE
HET CME A 161 10
HET SO4 A 401 5
HET SO4 A 402 5
HET SO4 A 403 5
HET ERZ A 404 28
HETNAM CME S,S-(2-HYDROXYETHYL)THIOCYSTEINE
HETNAM SO4 SULFATE ION
HETNAM ERZ ~{N}-(1,5-DIMETHYLPYRAZOL-4-YL)-5-METHYL-PYRIMIDIN-2-
HETNAM 2 ERZ AMINE
FORMUL 1 CME C5 H11 N O3 S2
FORMUL 2 SO4 3(O4 S 2-)
FORMUL 5 ERZ C10 H13 N5
FORMUL 6 HOH *522(H2 O)
HELIX 1 AA1 HIS A 61 PHE A 78 1 18
HELIX 2 AA2 LEU A 112 GLN A 119 1 8
HELIX 3 AA3 SER A 122 ALA A 143 1 22
HELIX 4 AA4 LYS A 151 SER A 153 5 3
HELIX 5 AA5 ASP A 175 ASP A 179 5 5
HELIX 6 AA6 THR A 190 ARG A 194 5 5
HELIX 7 AA7 ALA A 195 ASN A 201 1 7
HELIX 8 AA8 LYS A 207 ASN A 224 1 18
HELIX 9 AA9 LEU A 234 GLY A 245 1 12
HELIX 10 AB1 SER A 248 CYS A 254 1 7
HELIX 11 AB2 ASN A 257 LEU A 267 1 11
HELIX 12 AB3 PRO A 274 PHE A 279 1 6
HELIX 13 AB4 ASP A 283 LEU A 294 1 12
HELIX 14 AB5 GLU A 303 ALA A 309 1 7
HELIX 15 AB6 HIS A 310 GLU A 314 5 5
HELIX 16 AB7 ASP A 318 GLU A 322 5 5
HELIX 17 AB8 PRO A 339 THR A 351 1 13
HELIX 18 AB9 ALA A 352 GLN A 355 5 4
SHEET 1 AA1 5 TYR A 25 GLU A 33 0
SHEET 2 AA1 5 MET A 38 ASP A 44 -1 O TYR A 43 N THR A 26
SHEET 3 AA1 5 VAL A 49 ILE A 56 -1 O ILE A 53 N CYS A 40
SHEET 4 AA1 5 VAL A 101 ASP A 106 -1 O VAL A 101 N ILE A 56
SHEET 5 AA1 5 ASP A 88 ILE A 90 -1 N ASP A 88 O VAL A 104
SHEET 1 AA2 3 THR A 110 ASP A 111 0
SHEET 2 AA2 3 LEU A 155 LEU A 157 -1 O LEU A 157 N THR A 110
SHEET 3 AA2 3 LEU A 163 ILE A 165 -1 O LYS A 164 N LEU A 156
SHEET 1 AA3 2 VAL A 145 LEU A 146 0
SHEET 2 AA3 2 ARG A 172 VAL A 173 -1 O ARG A 172 N LEU A 146
LINK C THR A 160 N CME A 161 1555 1555 1.32
LINK C CME A 161 N ASP A 162 1555 1555 1.36
CISPEP 1 GLY A 22 PRO A 23 0 0.15
SITE 1 AC1 7 ARG A 191 ARG A 194 TYR A 233 HOH A 600
SITE 2 AC1 7 HOH A 626 HOH A 645 HOH A 760
SITE 1 AC2 1 ARG A 191
SITE 1 AC3 4 LYS A 207 HOH A 598 HOH A 652 HOH A 766
SITE 1 AC4 7 ALA A 52 GLN A 105 ASP A 106 MET A 108
SITE 2 AC4 7 GLU A 109 LYS A 114 HOH A 724
CRYST1 48.794 71.011 60.178 90.00 108.98 90.00 P 1 21 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 0.020494 0.000000 0.007049 0.00000
SCALE2 0.000000 0.014082 0.000000 0.00000
SCALE3 0.000000 0.000000 0.017573 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
