PDBsum entry 4jec

Hydrolase/hydrolase inhibitor

PDB id: 4jec

Contents

Protein chains

99 a.a.

Ligands

478

DOD ×131

Metals

_CL

PDB id:

4jec

Name:

Hydrolase/hydrolase inhibitor

Title:

Joint neutron and x-ray structure of per-deuterated HIV-1 protease in complex with clinical inhibitor amprenavir

Structure:

HIV-1 protease. Chain: a, b. Fragment: unp residues 501-599. Synonym: protease, pr, retropepsin. Engineered: yes

Source:

Human immunodeficiency virus type 1. HIV-1. Organism_taxid: 11676. Gene: gag-pol. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.01Å R-factor: 0.194 R-free: 0.203

Authors:

A.Y.Kovalevsky,I.T.Weber,P.Langan

Key ref:

I.T.Weber et al. (2013). Joint X-ray/neutron crystallographic study of HIV-1 protease with clinical inhibitor amprenavir: insights for drug design. J Med Chem, 56, 5631-5635. PubMed id: 23772563 DOI: 10.1021/jm400684f

Date:

26-Feb-13 Release date: 24-Jul-13

Protein chains

P03367  (POL_HV1BR) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI)

Seq: 1447 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 5 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: 10.1021/jm400684f

J Med Chem 56:5631-5635 (2013)

PubMed id: 23772563

Joint X-ray/neutron crystallographic study of HIV-1 protease with clinical inhibitor amprenavir: insights for drug design.

I.T.Weber, M.J.Waltman, M.Mustyakimov, M.P.Blakeley, D.A.Keen, A.K.Ghosh, P.Langan, A.Y.Kovalevsky.

ABSTRACT

HIV-1 protease is an important target for the development of antiviral inhibitors to treat AIDS. A room-temperature joint X-ray/neutron structure of the protease in complex with clinical drug amprenavir has been determined at 2.0 Å resolution. The structure provides direct determination of hydrogen atom positions in the enzyme active site. Analysis of the enzyme-drug interactions suggests that some hydrogen bonds may be weaker than deduced from the non-hydrogen interatomic distances. This information may be valuable for the design of improved protease inhibitors.