HEADER HYDROLASE/HYDROLASE INHIBITOR 08-FEB-11 3QN8
TITLE HIV-1 PROTEASE (MUTANT Q7K L33I L63I) IN COMPLEX WITH A NOVEL
TITLE 2 INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: PROTEASE;
COMPND 3 CHAIN: A, B;
COMPND 4 SYNONYM: PR, RETROPEPSIN;
COMPND 5 EC: 3.4.23.16;
COMPND 6 ENGINEERED: YES;
COMPND 7 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (BRU
SOURCE 3 ISOLATE);
SOURCE 4 ORGANISM_COMMON: HIV-1;
SOURCE 5 ORGANISM_TAXID: 11686;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562;
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 9 EXPRESSION_SYSTEM_PLASMID: PET24A
KEYWDS ASPARTYL PROTEASE, HYDROLASE-HYDROLASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR I.LINDEMANN,A.HEINE,G.KLEBE
REVDAT 2 01-NOV-23 3QN8 1 REMARK SEQADV
REVDAT 1 08-FEB-12 3QN8 0
JRNL AUTH I.LINDEMANN,N.KLEE,A.HEINE,W.E.DIEDERICH,G.KLEBE
JRNL TITL NOVEL INHIBITORS FOR HIV-1 PROTEASE
JRNL REF TO BE PUBLISHED
JRNL REFN
REMARK 2
REMARK 2 RESOLUTION. 1.38 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX (PHENIX.REFINE: 1.6.4_486)
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 : ML
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.38
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 29.18
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 95.6
REMARK 3 NUMBER OF REFLECTIONS : 46683
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.153
REMARK 3 R VALUE (WORKING SET) : 0.149
REMARK 3 FREE R VALUE : 0.181
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 10.060
REMARK 3 FREE R VALUE TEST SET COUNT : 4696
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 29.1865 - 2.9757 0.98 4525 504 0.1585 0.1860
REMARK 3 2 2.9757 - 2.3622 0.99 4430 499 0.1628 0.1863
REMARK 3 3 2.3622 - 2.0637 0.99 4411 454 0.1463 0.1727
REMARK 3 4 2.0637 - 1.8751 0.98 4279 487 0.1263 0.1546
REMARK 3 5 1.8751 - 1.7407 0.97 4257 465 0.1222 0.1755
REMARK 3 6 1.7407 - 1.6381 0.96 4184 498 0.1222 0.1589
REMARK 3 7 1.6381 - 1.5560 0.95 4105 471 0.1234 0.1726
REMARK 3 8 1.5560 - 1.4883 0.94 4090 463 0.1429 0.1891
REMARK 3 9 1.4883 - 1.4310 0.92 3984 439 0.1684 0.2163
REMARK 3 10 1.4310 - 1.3816 0.87 3722 416 0.2149 0.2561
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL
REMARK 3 SOLVENT RADIUS : 1.20
REMARK 3 SHRINKAGE RADIUS : 0.95
REMARK 3 K_SOL : 0.37
REMARK 3 B_SOL : 46.69
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.180
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 15.560
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 14.27
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 19.30
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -1.22070
REMARK 3 B22 (A**2) : 3.49400
REMARK 3 B33 (A**2) : -2.27320
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 0.00000
REMARK 3 B23 (A**2) : 0.00000
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 : 0.006 1688
REMARK 3 ANGLE : 1.228 2325
REMARK 3 CHIRALITY : 0.068 281
REMARK 3 PLANARITY : 0.006 294
REMARK 3 DIHEDRAL : 13.068 671
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 3QN8 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 17-FEB-11.
REMARK 100 THE DEPOSITION ID IS D_1000063857.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 24-JUN-10
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 5.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : BESSY
REMARK 200 BEAMLINE : 14.2
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.91841
REMARK 200 MONOCHROMATOR : DOUBLE CRYSTAL MONOCHROMATOR KMC
REMARK 200 -2
REMARK 200 OPTICS : MIRRORS
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : RAYONIX MX-225
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 47925
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.380
REMARK 200 RESOLUTION RANGE LOW (A) : 30.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 200 DATA REDUNDANCY : 5.000
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : 0.03800
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 38.6000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.38
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.40
REMARK 200 COMPLETENESS FOR SHELL (%) : 100.0
REMARK 200 DATA REDUNDANCY IN SHELL : 4.30
REMARK 200 R MERGE FOR SHELL (I) : NULL
REMARK 200 R SYM FOR SHELL (I) : 0.36500
REMARK 200 <I/SIGMA(I)> FOR SHELL : 3.600
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: 2PQZ
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 54.59
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.71
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 500MM NACL, 100MM NA CITRATE, 100MM
REMARK 280 DTT, 3MM NAN3, PH 5.5, VAPOR DIFFUSION, SITTING DROP,
REMARK 280 TEMPERATURE 289K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 2
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,-Y,Z
REMARK 290 3555 -X+1/2,Y+1/2,-Z
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 0.00000
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 29.18000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 42.83000
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 29.18000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 42.83000
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: DIMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 3560 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 9660 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -24.0 KCAL/MOL
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, 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 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 LYS A 7 CG CD CE NZ
REMARK 470 ARG A 41 CG CD NE CZ NH1 NH2
REMARK 470 LYS B 43 CG CD CE NZ
REMARK 470 LYS B 55 CG CD CE NZ
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CL A 100
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NI7 B 100
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CL B 101
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CL B 102
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 3QIH RELATED DB: PDB
REMARK 900 HIV-1 PROTEASE (MUTANT Q7K L33I L63I) IN COMPLEX WITH A NOVEL
REMARK 900 INHIBITOR
DBREF 3QN8 A 1 99 UNP P03367 POL_HV1BR 501 599
DBREF 3QN8 B 1 99 UNP P03367 POL_HV1BR 501 599
SEQADV 3QN8 LYS A 7 UNP P03367 GLN 507 ENGINEERED MUTATION
SEQADV 3QN8 ILE A 33 UNP P03367 LEU 533 ENGINEERED MUTATION
SEQADV 3QN8 ILE A 63 UNP P03367 LEU 563 ENGINEERED MUTATION
SEQADV 3QN8 LYS B 7 UNP P03367 GLN 507 ENGINEERED MUTATION
SEQADV 3QN8 ILE B 33 UNP P03367 LEU 533 ENGINEERED MUTATION
SEQADV 3QN8 ILE B 63 UNP P03367 LEU 563 ENGINEERED MUTATION
SEQRES 1 A 99 PRO GLN ILE THR LEU TRP LYS ARG PRO LEU VAL THR ILE
SEQRES 2 A 99 LYS ILE GLY GLY GLN LEU LYS GLU ALA LEU LEU ASP THR
SEQRES 3 A 99 GLY ALA ASP ASP THR VAL ILE GLU GLU MET SER LEU PRO
SEQRES 4 A 99 GLY ARG TRP LYS PRO LYS MET ILE GLY GLY ILE GLY GLY
SEQRES 5 A 99 PHE ILE LYS VAL ARG GLN TYR ASP GLN ILE ILE ILE GLU
SEQRES 6 A 99 ILE CYS GLY HIS LYS ALA ILE GLY THR VAL LEU VAL GLY
SEQRES 7 A 99 PRO THR PRO VAL ASN ILE ILE GLY ARG ASN LEU LEU THR
SEQRES 8 A 99 GLN ILE GLY CYS THR LEU ASN PHE
SEQRES 1 B 99 PRO GLN ILE THR LEU TRP LYS ARG PRO LEU VAL THR ILE
SEQRES 2 B 99 LYS ILE GLY GLY GLN LEU LYS GLU ALA LEU LEU ASP THR
SEQRES 3 B 99 GLY ALA ASP ASP THR VAL ILE GLU GLU MET SER LEU PRO
SEQRES 4 B 99 GLY ARG TRP LYS PRO LYS MET ILE GLY GLY ILE GLY GLY
SEQRES 5 B 99 PHE ILE LYS VAL ARG GLN TYR ASP GLN ILE ILE ILE GLU
SEQRES 6 B 99 ILE CYS GLY HIS LYS ALA ILE GLY THR VAL LEU VAL GLY
SEQRES 7 B 99 PRO THR PRO VAL ASN ILE ILE GLY ARG ASN LEU LEU THR
SEQRES 8 B 99 GLN ILE GLY CYS THR LEU ASN PHE
HET CL A 100 1
HET NI7 B 100 27
HET CL B 101 1
HET CL B 102 1
HETNAM CL CHLORIDE ION
HETNAM NI7 (4AS,7AS)-1,4-BIS(3-HYDROXYBENZYL)HEXAHYDRO-1H-
HETNAM 2 NI7 PYRROLO[3,4-B]PYRAZINE-2,3-DIONE
FORMUL 3 CL 3(CL 1-)
FORMUL 4 NI7 C20 H21 N3 O4
FORMUL 7 HOH *294(H2 O)
HELIX 1 1 GLY A 86 THR A 91 1 6
HELIX 2 2 GLN A 92 GLY A 94 5 3
HELIX 3 3 GLY B 86 ILE B 93 1 8
SHEET 1 A 4 GLN A 2 ILE A 3 0
SHEET 2 A 4 THR B 96 ASN B 98 -1 O LEU B 97 N ILE A 3
SHEET 3 A 4 THR A 96 ASN A 98 -1 N THR A 96 O ASN B 98
SHEET 4 A 4 GLN B 2 ILE B 3 -1 O ILE B 3 N LEU A 97
SHEET 1 B 8 TRP A 42 GLY A 49 0
SHEET 2 B 8 GLY A 52 ILE A 66 -1 O GLN A 58 N LYS A 43
SHEET 3 B 8 HIS A 69 VAL A 77 -1 O HIS A 69 N ILE A 66
SHEET 4 B 8 VAL A 32 ILE A 33 1 N ILE A 33 O LEU A 76
SHEET 5 B 8 ILE A 84 ILE A 85 -1 O ILE A 84 N VAL A 32
SHEET 6 B 8 GLN A 18 LEU A 24 1 N LEU A 23 O ILE A 85
SHEET 7 B 8 LEU A 10 ILE A 15 -1 N ILE A 13 O LYS A 20
SHEET 8 B 8 GLY A 52 ILE A 66 -1 O GLU A 65 N LYS A 14
SHEET 1 C 8 LYS B 43 GLY B 49 0
SHEET 2 C 8 GLY B 52 ILE B 66 -1 O VAL B 56 N LYS B 45
SHEET 3 C 8 HIS B 69 VAL B 77 -1 O HIS B 69 N ILE B 66
SHEET 4 C 8 VAL B 32 ILE B 33 1 N ILE B 33 O LEU B 76
SHEET 5 C 8 ILE B 84 ILE B 85 -1 O ILE B 84 N VAL B 32
SHEET 6 C 8 GLN B 18 LEU B 24 1 N LEU B 23 O ILE B 85
SHEET 7 C 8 LEU B 10 ILE B 15 -1 N ILE B 13 O LYS B 20
SHEET 8 C 8 GLY B 52 ILE B 66 -1 O GLU B 65 N LYS B 14
SITE 1 AC1 5 THR A 74 ASN A 88 HOH A 105 HOH A 156
SITE 2 AC1 5 ARG B 41
SITE 1 AC2 23 ASP A 25 GLY A 27 ALA A 28 ASP A 29
SITE 2 AC2 23 ASP A 30 VAL A 32 GLY A 48 GLY A 49
SITE 3 AC2 23 ILE A 50 ILE A 84 HOH A 149 ASP B 25
SITE 4 AC2 23 ALA B 28 ASP B 29 ASP B 30 VAL B 32
SITE 5 AC2 23 GLY B 49 ILE B 50 HOH B 140 HOH B 164
SITE 6 AC2 23 HOH B 175 HOH B 196 HOH B 375
SITE 1 AC3 1 TRP B 6
SITE 1 AC4 3 THR B 74 ASN B 88 HOH B 154
CRYST1 58.360 85.660 46.840 90.00 90.00 90.00 P 21 21 2 8
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 0.017135 0.000000 0.000000 0.00000
SCALE2 0.000000 0.011674 0.000000 0.00000
SCALE3 0.000000 0.000000 0.021349 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
