PDBsum entry: 1a5x

Hydrolase

PDB id: 1a5x

Contents

Protein chain

146 a.a. *

Ligands

_Y3

Waters ×169

* Residue conservation analysis

PDB id:

1a5x

Name:

Hydrolase

Title:

Asv integrase core domain with HIV-1 integrase inhibitor y3

Structure:

Integrase. Chain: a. Fragment: catalytic core domain. Engineered: yes. Other_details: p03354 fragment of polyprotein pol-rsvp

Source:

Rous sarcoma virus (strain schmidt- ruppin). Organism_taxid: 11889. Strain: schmidt-ruppin. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: see jrnl reference

Biol. unit:

Dimer (from PDB file)

Resolution:

1.90Å R-factor: 0.155 R-free: 0.212

Authors:

J.Lubkowski,F.Yang,J.Alexandratos,A.Wlodawer

Key ref:

J.Lubkowski et al. (1998). Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor. Proc Natl Acad Sci U S A, 95, 4831-4836. PubMed id: 9560188 DOI: 10.1073/pnas.95.9.4831

Date:

18-Feb-98 Release date: 27-May-98

Protein chain

O92956  (POL_RSVSB) -  Gag-Pro-Pol polyprotein

Seq: 1603 a.a.

Struc: 147 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 2: E.C.2.7.7.49 - RNA-directed Dna polymerase.
• Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
• Enzyme class 3: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
• Enzyme class 4: E.C.3.1.26.4 - Ribonuclease H.
• Reaction: Endonucleolytic cleavage to 5'-phosphomonoester.

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

 Gene Ontology (GO) functional annotation 

• Biological process: DNA integration (1 term)
• Biochemical function: nucleic acid binding (2 terms)

reference

DOI no: 10.1073/pnas.95.9.4831

Proc Natl Acad Sci U S A 95:4831-4836 (1998)

PubMed id: 9560188

Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor.

J.Lubkowski, F.Yang, J.Alexandratos, A.Wlodawer, H.Zhao, T.R.Burke, N.Neamati, Y.Pommier, G.Merkel, A.M.Skalka.

ABSTRACT

The x-ray structures of an inhibitor complex of the catalytic core domain of avian sarcoma virus integrase (ASV IN) were solved at 1.9- to 2.0-A resolution at two pH values, with and without Mn2+ cations. This inhibitor (Y-3), originally identified in a screen for inhibitors of the catalytic activity of HIV type 1 integrase (HIV-1 IN), was found in the present study to be active against ASV IN as well as HIV-1 IN. The Y-3 molecule is located in close proximity to the enzyme active site, interacts with the flexible loop, alters loop conformation, and affects the conformations of active site residues. As crystallized, a Y-3 molecule stacks against its symmetry-related mate. Preincubation of IN with metal cations does not prevent inhibition, and Y-3 binding does not prevent binding of divalent cations to IN. Three compounds chemically related to Y-3 also were investigated, but no binding was observed in the crystals. Our results identify the structural elements of the inhibitor that likely determine its binding properties.

Selected figure(s)

Figure 3.
Fig. 3. An electron density (ED) map for the inhibitor Y-3. The initial F[o]-F[c] ED map is contoured at the 2.5 level (red); the final 2F[o]-F[c] ED map is contoured at the 1.1 level (blue). The refined conformation of the Y-3 model is shown in green. Prepared with BOBSCRIPT, a modification of MOLSCRIPT (36).

Figure 5.
Fig. 5. Inhibitor binding site. Conformational differences between the Y-3- ASV IN (core) complex [pH 5.6 (green)] and the unliganded enzyme, Protein Data Bank code 1ASV (magenta). (A) Residues with altered conformation are labeled. For Arg 158, one of two alternate conformations is shown. The bound Y-3 molecule and its symmetry-related copy are both shown. (B) Conformational changes in the flexible loop sections (residues 141-146) with bound inhibitor molecules.

Figures were selected by the author.