Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T56915 Target Info
Target Name Human immunodeficiency virus Protease (HIV PR)
Synonyms HIV Retropepsin; HIV PR
Target Type Successful Target
Gene Name HIV PR
Biochemical Class Peptidase
UniProt ID
POL_HV1B1
Ligand General Information  Top
Ligand Name (3r,3as,6as)-4,4-Difluorohexahydrofuro[2,3-B]furan-3-Yl [(2s,3r)-4-{[(4-Aminophenyl)sulfonyl](2-Methylpropyl)amino}-3-Hydroxy-1-Phenylbutan-2-Yl]carbamate Ligand Info
Canonical SMILES CC(C)CN(CC(C(CC1=CC=CC=C1)NC(=O)OC2COC3C2C(CO3)(F)F)O)S(=O)(=O)C4=CC=C(C=C4)N
InChI 1S/C27H35F2N3O7S/c1-17(2)13-32(40(35,36)20-10-8-19(30)9-11-20)14-22(33)21(12-18-6-4-3-5-7-18)31-26(34)39-23-15-37-25-24(23)27(28,29)16-38-25/h3-11,17,21-25,33H,12-16,30H2,1-2H3,(H,31,34)/t21-,22+,23-,24-,25-/m0/s1
InChIKey UQYAKJSDOQPRAX-YCXOGWGTSA-N
PubChem Compound ID 86223086
Drug Binding Sites of Target  Top
PDB ID: 4U8W      HIV-1 wild Type protease with GRL-050-10A (a Gem-difluoro-bis-Tetrahydrofuran as P2-Ligand)
Method X-ray diffraction Resolution 1.30 Å Mutation Yes [1]
PDB Sequence
PQITLWKRPL
10
VTIKIGGQLK
20
EALLDTGADD
30
TVIEEMSLPG
40
RWKPKMIGGI
50

GGFIKVRQYD
60
QIIIEIAGHK
70
AIGTVLVGPT
80
PVNIIGRNLL
90
TQIGATLNF
Residue
Distance (Å)
ARG8
3.988
LEU23
3.775
ASP25
2.500
GLY27
3.379
ALA28
3.486
ASP29
4.237
ASP30
3.196
THR31
4.726
VAL32
3.480
Residue
Distance (Å)
ILE47
4.135
GLY48
2.776
GLY49
2.740
ILE50
3.437
LEU76
4.298
PRO81
3.696
VAL82
3.278
ILE84
3.273
PDB ID: 4YHQ      Crystal structure of multidrug resistant clinical isolate PR20 with GRL-5010A
Method X-ray diffraction Resolution 1.30 Å Mutation Yes [2]
PDB Sequence
PQITLWKRPF
10
VTVKVGGQLK
20
EALLDTGADN
30
TIFEDINLPG
40
RWKPKMVGGI
50

GGFLKVREYD
60
QVPIEIAGHK
70
VIGTVLVGPT
80
PVNVIGRDTM
90
TQIGATLNF
Residue
Distance (Å)
LEU23
3.750
ASP25
2.951
GLY27
2.986
ALA28
3.683
ASP29
2.926
ASN30
3.267
ILE32
3.982
Residue
Distance (Å)
VAL47
3.962
GLY48
2.119
GLY49
3.422
ILE50
2.756
VAL82
3.695
VAL84
4.266
References  Top
REF 1 Design of gem-difluoro-bis-tetrahydrofuran as P2 ligand for HIV-1 protease inhibitors to improve brain penetration: synthesis, X-ray studies, and biological evaluation. ChemMedChem. 2015 Jan;10(1):107-15.
REF 2 Substituted Bis-THF Protease Inhibitors with Improved Potency against Highly Resistant Mature HIV-1 Protease PR20. J Med Chem. 2015 Jun 25;58(12):5088-95.

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