HEADER ISOMERASE/ISOMERASE INHIBITOR 21-MAY-20 6X3Y
TITLE HUMAN CYCLOPHILIN A BOUND TO A SERIES OF ACYLCIC AND MACROCYCLIC
TITLE 2 INHIBITORS
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: PEPTIDYL-PROLYL CIS-TRANS ISOMERASE A;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: PPIASE A,CYCLOPHILIN A,CYCLOSPORIN A-BINDING PROTEIN,
COMPND 5 ROTAMASE A;
COMPND 6 EC: 5.2.1.8;
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: PPIA, CYPA;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS CYCLOPHILIN A, SANGLIFEHRIN A, PROLYL ISOMERASE, MACROCYLCIC
KEYWDS 2 INHIBITOR, PEPTIDOMIMETIC, ISOMERASE-ISOMERASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR T.C.APPLEBY,J.L.PAULSEN,U.SCHMITZ,D.SHIVAKUMAR
REVDAT 4 18-OCT-23 6X3Y 1 REMARK
REVDAT 3 26-AUG-20 6X3Y 1 JRNL
REVDAT 2 01-JUL-20 6X3Y 1 JRNL
REVDAT 1 24-JUN-20 6X3Y 0
JRNL AUTH J.L.PAULSEN,H.S.YU,D.SINDHIKARA,L.WANG,T.APPLEBY,
JRNL AUTH 2 A.G.VILLASENOR,U.SCHMITZ,D.SHIVAKUMAR
JRNL TITL EVALUATION OF FREE ENERGY CALCULATIONS FOR THE
JRNL TITL 2 PRIORITIZATION OF MACROCYCLE SYNTHESIS.
JRNL REF J.CHEM.INF.MODEL. V. 60 3489 2020
JRNL REFN ESSN 1549-960X
JRNL PMID 32539379
JRNL DOI 10.1021/ACS.JCIM.0C00132
REMARK 2
REMARK 2 RESOLUTION. 1.40 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX 1.17.1_3660
REMARK 3 AUTHORS : PAUL ADAMS,PAVEL AFONINE,VINCENT CHEN,IAN
REMARK 3 : DAVIS,KRESHNA GOPAL,RALF GROSSE-KUNSTLEVE,
REMARK 3 : LI-WEI HUNG,ROBERT IMMORMINO,TOM IOERGER,
REMARK 3 : AIRLIE MCCOY,ERIK MCKEE,NIGEL MORIARTY,
REMARK 3 : REETAL PAI,RANDY READ,JANE RICHARDSON,
REMARK 3 : DAVID RICHARDSON,TOD ROMO,JIM SACCHETTINI,
REMARK 3 : NICHOLAS SAUTER,JACOB SMITH,LAURENT
REMARK 3 : STORONI,TOM TERWILLIGER,PETER ZWART
REMARK 3
REMARK 3 REFINEMENT TARGET : GEOSTD + MONOMER LIBRARY + CDL V1.2
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.40
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 34.10
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.380
REMARK 3 COMPLETENESS FOR RANGE (%) : 96.2
REMARK 3 NUMBER OF REFLECTIONS : 38734
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.156
REMARK 3 R VALUE (WORKING SET) : 0.155
REMARK 3 FREE R VALUE : 0.171
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.160
REMARK 3 FREE R VALUE TEST SET COUNT : 2000
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT (IN BINS).
REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK RFREE
REMARK 3 1 34.1000 - 3.3700 0.91 2667 146 0.1445 0.1496
REMARK 3 2 3.3700 - 2.6800 0.96 2676 145 0.1612 0.1809
REMARK 3 3 2.6800 - 2.3400 0.97 2678 146 0.1730 0.2005
REMARK 3 4 2.3400 - 2.1300 0.98 2671 145 0.1631 0.1820
REMARK 3 5 2.1200 - 1.9700 0.97 2677 146 0.1549 0.1882
REMARK 3 6 1.9700 - 1.8600 0.98 2657 144 0.1580 0.1545
REMARK 3 7 1.8600 - 1.7600 0.98 2638 144 0.1578 0.1694
REMARK 3 8 1.7600 - 1.6900 0.97 2637 144 0.1488 0.1720
REMARK 3 9 1.6900 - 1.6200 0.97 2599 141 0.1385 0.1714
REMARK 3 10 1.6200 - 1.5700 0.96 2609 143 0.1458 0.1409
REMARK 3 11 1.5700 - 1.5200 0.96 2571 139 0.1355 0.1508
REMARK 3 12 1.5200 - 1.4700 0.96 2582 141 0.1467 0.1623
REMARK 3 13 1.4700 - 1.4300 0.96 2574 140 0.1526 0.1653
REMARK 3 14 1.4300 - 1.4000 0.93 2498 136 0.1642 0.1811
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL
REMARK 3 SOLVENT RADIUS : 1.11
REMARK 3 SHRINKAGE RADIUS : 0.90
REMARK 3 K_SOL : NULL
REMARK 3 B_SOL : NULL
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.084
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 15.074
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 11.03
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 14.12
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 TWINNING INFORMATION.
REMARK 3 FRACTION: NULL
REMARK 3 OPERATOR: NULL
REMARK 3
REMARK 3 DEVIATIONS FROM IDEAL VALUES.
REMARK 3 RMSD COUNT
REMARK 3 BOND : 0.008 1327
REMARK 3 ANGLE : 1.119 1787
REMARK 3 CHIRALITY : 0.098 183
REMARK 3 PLANARITY : 0.007 236
REMARK 3 DIHEDRAL : 5.981 175
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 NCS DETAILS
REMARK 3 NUMBER OF NCS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 6X3Y COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 22-MAY-20.
REMARK 100 THE DEPOSITION ID IS D_1000249555.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 25-AUG-10
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 8.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : ALS
REMARK 200 BEAMLINE : 5.0.1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.976
REMARK 200 MONOCHROMATOR : SI(220)
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 40383
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.400
REMARK 200 RESOLUTION RANGE LOW (A) : 34.100
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 96.3
REMARK 200 DATA REDUNDANCY : 6.100
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : 0.06400
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 25.3100
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.40
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.44
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) : 0.22100
REMARK 200 <I/SIGMA(I)> FOR SHELL : NULL
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: PHASER
REMARK 200 STARTING MODEL: PDB ENTRY 2CPL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 55.11
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.74
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 20 MM TRIS-HCL, PH 8.5, 2 MM DTT, 2 MM
REMARK 280 EDTA, 20-35% PEG3350, 5% ETHANOL, VAPOR DIFFUSION, HANGING DROP,
REMARK 280 TEMPERATURE 277K
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 21.19650
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 44.71950
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 26.34900
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 44.71950
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 21.19650
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 26.34900
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: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 0 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 7680 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: 0.0 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 GLU A 165
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 MET A 1 CG SD CE
REMARK 470 GLU A 15 CG CD OE1 OE2
REMARK 470 LYS A 125 CE NZ
REMARK 470 LYS A 131 CD CE NZ
REMARK 470 LYS A 133 CE NZ
REMARK 470 LYS A 151 CD CE NZ
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 PHE A 60 -76.49 -137.82
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 A 962 DISTANCE = 6.41 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue UMM A 600
DBREF 6X3Y A 1 165 UNP P62937 PPIA_HUMAN 1 165
SEQADV 6X3Y GLY A -1 UNP P62937 EXPRESSION TAG
SEQADV 6X3Y HIS A 0 UNP P62937 EXPRESSION TAG
SEQRES 1 A 167 GLY HIS MET VAL ASN PRO THR VAL PHE PHE ASP ILE ALA
SEQRES 2 A 167 VAL ASP GLY GLU PRO LEU GLY ARG VAL SER PHE GLU LEU
SEQRES 3 A 167 PHE ALA ASP LYS VAL PRO LYS THR ALA GLU ASN PHE ARG
SEQRES 4 A 167 ALA LEU SER THR GLY GLU LYS GLY PHE GLY TYR LYS GLY
SEQRES 5 A 167 SER CYS PHE HIS ARG ILE ILE PRO GLY PHE MET CYS GLN
SEQRES 6 A 167 GLY GLY ASP PHE THR ARG HIS ASN GLY THR GLY GLY LYS
SEQRES 7 A 167 SER ILE TYR GLY GLU LYS PHE GLU ASP GLU ASN PHE ILE
SEQRES 8 A 167 LEU LYS HIS THR GLY PRO GLY ILE LEU SER MET ALA ASN
SEQRES 9 A 167 ALA GLY PRO ASN THR ASN GLY SER GLN PHE PHE ILE CYS
SEQRES 10 A 167 THR ALA LYS THR GLU TRP LEU ASP GLY LYS HIS VAL VAL
SEQRES 11 A 167 PHE GLY LYS VAL LYS GLU GLY MET ASN ILE VAL GLU ALA
SEQRES 12 A 167 MET GLU ARG PHE GLY SER ARG ASN GLY LYS THR SER LYS
SEQRES 13 A 167 LYS ILE THR ILE ALA ASP CYS GLY GLN LEU GLU
HET UMM A 600 39
HETNAM UMM TERT-BUTYL [(2S)-1-{[(3S,17S)-2,16-DIOXO-10,15-DIOXA-1,
HETNAM 2 UMM 21-DIAZATRICYCLO[15.3.1.1~5,9~]DOCOSA-5(22),6,8-TRIEN-
HETNAM 3 UMM 3-YL]AMINO}-3-METHYL-1-OXOBUTAN-2-YL]CARBAMATE
FORMUL 2 UMM C28 H42 N4 O7
FORMUL 3 HOH *262(H2 O)
HELIX 1 AA1 VAL A 29 GLY A 42 1 14
HELIX 2 AA2 THR A 119 ASP A 123 5 5
HELIX 3 AA3 GLY A 135 ARG A 144 1 10
SHEET 1 AA1 8 ARG A 55 ILE A 57 0
SHEET 2 AA1 8 MET A 61 GLY A 64 -1 O GLN A 63 N ARG A 55
SHEET 3 AA1 8 PHE A 112 CYS A 115 -1 O ILE A 114 N CYS A 62
SHEET 4 AA1 8 ILE A 97 MET A 100 -1 N ILE A 97 O CYS A 115
SHEET 5 AA1 8 VAL A 128 GLU A 134 -1 O GLY A 130 N LEU A 98
SHEET 6 AA1 8 GLU A 15 LEU A 24 -1 N SER A 21 O LYS A 133
SHEET 7 AA1 8 THR A 5 VAL A 12 -1 N ILE A 10 O GLY A 18
SHEET 8 AA1 8 ILE A 156 GLN A 163 -1 O ASP A 160 N ASP A 9
SITE 1 AC1 18 ARG A 55 ILE A 57 PHE A 60 MET A 61
SITE 2 AC1 18 GLN A 63 ASP A 85 GLU A 86 ASN A 87
SITE 3 AC1 18 PHE A 88 ALA A 101 ASN A 102 ALA A 103
SITE 4 AC1 18 PHE A 113 HIS A 126 HOH A 717 HOH A 787
SITE 5 AC1 18 HOH A 809 HOH A 833
CRYST1 42.393 52.698 89.439 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 0.023589 0.000000 0.000000 0.00000
SCALE2 0.000000 0.018976 0.000000 0.00000
SCALE3 0.000000 0.000000 0.011181 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
