PDBsum entry 1hii

Hydrolase (aspartic proteinase)

PDB id: 1hii

Contents

Protein chains

99 a.a. *

Ligands

SO4 ×2

C20

Waters ×194

* Residue conservation analysis

PDB id:

1hii

Name:

Hydrolase (aspartic proteinase)

Title:

Comparative analysis of the x-ray structures of HIV-1 and HIV-2 proteases in complex with cgp 53820, a novel pseudosymmetric inhibitor

Structure:

HIV-2 protease. Chain: a, b. Engineered: yes

Source:

Human immunodeficiency virus 2. Organism_taxid: 11709. Cell_line: s2. Gene: pol. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.30Å R-factor: 0.138

Authors:

J.P.Priestle,M.G.Gruetter

Key ref:

J.P.Priestle et al. (1995). Comparative analysis of the X-ray structures of HIV-1 and HIV-2 proteases in complex with CGP 53820, a novel pseudosymmetric inhibitor. Structure, 3, 381-389. PubMed id: 7613867 DOI: 10.1016/S0969-2126(01)00169-1

Date:

31-Mar-95 Release date: 10-Jul-95

Protein chains

P04584  (POL_HV2RO) -  Gag-Pol polyprotein from Human immunodeficiency virus type 2 subtype A (isolate ROD)

Seq: 1464 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.3.4.23.47 - HIV-2 retropepsin.

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/S0969-2126(01)00169-1

Structure 3:381-389 (1995)

PubMed id: 7613867

Comparative analysis of the X-ray structures of HIV-1 and HIV-2 proteases in complex with CGP 53820, a novel pseudosymmetric inhibitor.

J.P.Priestle, A.Fässler, J.Rösel, M.Tintelnot-Blomley, P.Strop, M.G.Grütter.

ABSTRACT

BACKGROUND: The human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). Two subtypes of the virus, HIV-1 and HIV-2, have been characterized. The protease enzymes from these two subtypes, which are aspartic acid proteases and have been found to be essential for maturation of the infectious particle, share about 50% sequence identity. Differences in substrate and inhibitor binding between these enzymes have been previously reported. RESULTS: We report the X-ray crystal structures of both HIV-1 and HIV-2 proteases each in complex with the pseudosymmetric inhibitor, CGP 53820, to 2.2 A and 2.3 A, respectively. In both structures, the entire enzyme and inhibitor could be located. The structures confirmed earlier modeling studies. Differences between the CGP 53820 inhibitory binding constants for the two enzymes could be correlated with structural differences. CONCLUSIONS: Minor sequence changes in subsites at the active site can explain some of the observed differences in substrate and inhibitor binding between the two enzymes. The information gained from this investigation may help in the design of equipotent HIV-1/HIV-2 protease inhibitors.

Selected figure(s)

Figure 2.
Figure 2. The pseudosymmetrical HIV protease inhibitor CGP 53820. Cha refers to the cyclohexyl ‘side chain’ which binds in the P1′ pocket of HIV protease. Figure 2. The pseudosymmetrical HIV protease inhibitor CGP 53820. Cha refers to the cyclohexyl ‘side chain’ which binds in the P1′ pocket of HIV protease.

Figure 6.
Figure 6. Stereo illustration of the binding of CGP 53820 (green) to HIV-1 protease (red) superimposed with HIV-2 protease (blue) in complex with CGP 53820 (yellow). Figure 6. Stereo illustration of the binding of CGP 53820 (green) to HIV-1 protease (red) superimposed with HIV-2 protease (blue) in complex with CGP 53820 (yellow).

The above figures are reprinted by permission from Cell Press: Structure (1995, 3, 381-389) copyright 1995.

Figures were selected by an automated process.