PDBsum entry 6dv4

Hydrolase, antiviral protein

PDB id: 6dv4

Contents

Protein chains

99 a.a.

Ligands

GA5

ACT

GOL

Metals

_CL ×2

_NA

Waters ×142

PDB id:

6dv4

Name:

Hydrolase, antiviral protein

Title:

HIV-1 wild type protease with grl-04315a, a tetrahydronaphthalene carboxamide with (r)-boc-amine and (s)-hydroxyl functionalities as the p2 ligand

Structure:

Protease. Chain: a, b. Engineered: yes. Mutation: yes

Source:

Human immunodeficiency virus 1. Organism_taxid: 11676. Gene: pol. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008

Resolution:

1.14Å R-factor: 0.174 R-free: 0.196

Authors:

Y.-F.Wang,J.Agniswamy,I.T.Weber

Key ref:

A.K.Ghosh et al. (2018). Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands. Eur J Med Chem, 160, 171-182. PubMed id: 30340140 DOI: 10.1016/j.ejmech.2018.09.046

Date:

22-Jun-18 Release date: 31-Oct-18

Protein chains

P04585  (POL_HV1H2) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)

Seq: 1435 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.- - ?????
• Enzyme class 2: E.C.2.7.7.49 - RNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 3: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 4: E.C.3.1.-.-
• Enzyme class 5: E.C.3.1.13.2 - exoribonuclease H.
• Reaction: Exonucleolytic cleavage to 5'-phosphomonoester oligonucleotides in both 5'- to 3'- and 3'- to 5'-directions.
• Enzyme class 6: E.C.3.1.26.13 - retroviral ribonuclease H.
• Enzyme class 7: E.C.3.4.23.16 - HIV-1 retropepsin.
• Reaction: Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.ejmech.2018.09.046

Eur J Med Chem 160:171-182 (2018)

PubMed id: 30340140

Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands.

A.K.Ghosh, R.D.Jadhav, H.Simpson, S.Kovela, H.Osswald, J.Agniswamy, Y.F.Wang, S.I.Hattori, I.T.Weber, H.Mitsuya.

ABSTRACT

We describe the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors with carboxamide derivatives as the P2 ligands. We have specifically designed aminothiochromane and aminotetrahydronaphthalene-based carboxamide ligands to promote hydrogen bonding and van der Waals interactions in the active site of HIV-1 protease. Inhibitors 4e and 4j have shown potent enzyme inhibitory and antiviral activity. High resolution X-ray crystal structures of 4d- and 4k-bound HIV-1 protease revealed molecular insights into the ligand-binding site interactions.