PDBsum entry 2bbb

Hydrolase

PDB id: 2bbb

Contents

Protein chains

99 a.a. *

Ligands

HH1

Waters ×223

* Residue conservation analysis

PDB id:

2bbb

Name:

Hydrolase

Title:

Structure of hiv1 protease and hh1_173_3a complex.

Structure:

Protease. Chain: a, b. Engineered: yes

Source:

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

Biol. unit:

Dimer (from PQS)

Resolution:

1.70Å R-factor: 0.217 R-free: 0.229

Authors:

A.B.Smith Iii,A.K.Charnley,L.C.Kuo,S.Munshi

Key ref:

A.B.Smith et al. (2006). Design, synthesis, and biological evaluation of monopyrrolinone-based HIV-1 protease inhibitors possessing augmented P2' side chains. Bioorg Med Chem Lett, 16, 859-863. PubMed id: 16298527 DOI: 10.1016/j.bmcl.2005.11.011

Date:

17-Oct-05 Release date: 15-Nov-05

Protein chains

P03366  (POL_HV1B1) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate BH10)

Seq: 1447 a.a.

Struc: 99 a.a.

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.bmcl.2005.11.011

Bioorg Med Chem Lett 16:859-863 (2006)

PubMed id: 16298527

Design, synthesis, and biological evaluation of monopyrrolinone-based HIV-1 protease inhibitors possessing augmented P2' side chains.

A.B.Smith, A.K.Charnley, H.Harada, J.J.Beiger, L.D.Cantin, C.S.Kenesky, R.Hirschmann, S.Munshi, D.B.Olsen, M.W.Stahlhut, W.A.Schleif, L.C.Kuo.

ABSTRACT

A series of monopyrrolinone-based HIV-1 protease inhibitors possessing rationally designed P2' side chains have been synthesized and evaluated for activity against wild-type HIV-1 protease. The most potent inhibitor displays subnanomolar potency in vitro for the wild-type HIV-1 protease. Additionally, the monopyrrolinone inhibitors retain potency in cellular assays against clinically significant mutant forms of the virus. X-ray structures of these inhibitors bound in the wild-type enzyme reveal important insights into the observed biological activity.