PDBsum entry 1bdq

Hydrolase

PDB id: 1bdq

Contents

Protein chains

99 a.a. *

Ligands

IM1

Waters ×43

* Residue conservation analysis

PDB id:

1bdq

Name:

Hydrolase

Title:

HIV-1 (2:31-37, 47, 82) protease complexed with inhibitor sb203386

Structure:

HIV-1 protease. Chain: a, b. Engineered: yes. Mutation: yes

Source:

Human immunodeficiency virus 1. Organism_taxid: 11676. Strain: iiib. Gene: HIV-1 protease. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: bmh 71-18 muts.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.50Å R-factor: 0.191 R-free: 0.261

Authors:

M.A.Swairjo,S.S.Abdel-Meguid

Key ref:

M.A.Swairjo et al. (1998). Structural role of the 30's loop in determining the ligand specificity of the human immunodeficiency virus protease. Biochemistry, 37, 10928-10936. PubMed id: 9692985 DOI: 10.1021/bi980784h

Date:

10-May-98 Release date: 12-Aug-98

Protein chains

P04587  (POL_HV1B5) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate BH5)

Seq: 1447 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 9 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/bi980784h

Biochemistry 37:10928-10936 (1998)

PubMed id: 9692985

Structural role of the 30's loop in determining the ligand specificity of the human immunodeficiency virus protease.

M.A.Swairjo, E.M.Towler, C.Debouck, S.S.Abdel-Meguid.

ABSTRACT

The structural basis of ligand specificity in human immunodeficiency virus (HIV) protease has been investigated by determining the crystal structures of three chimeric HIV proteases complexed with SB203386, a tripeptide analogue inhibitor. The chimeras are constructed by substituting amino acid residues in the HIV type 1 (HIV-1) protease sequence with the corresponding residues from HIV type 2 (HIV-2) in the region spanning residues 31-37 and in the active site cavity. SB203386 is a potent inhibitor of HIV-1 protease (Ki = 18 nM) but has a decreased affinity for HIV-2 protease (Ki = 1280 nM). Crystallographic analysis reveals that substitution of residues 31-37 (30's loop) with those of HIV-2 protease renders the chimera similar to HIV-2 protease in both the inhibitor binding affinity and mode of binding (two inhibitor molecules per protease dimer). However, further substitution of active site residues 47 and 82 has a compensatory effect which restores the HIV-1-like inhibitor binding mode (one inhibitor molecule in the center of the protease active site) and partially restores the affinity. Comparison of the three chimeric protease structures with those of HIV-1 and SIV proteases complexed with the same inhibitor reveals structural changes in the flap regions and the 80's loops, as well as changes in the dimensions of the active site cavity. The study provides structural evidence of the role of the 30's loop in conferring inhibitor specificity in HIV proteases.