Home  |  Contact
PROSITE documentation PDOC50994 [for PROSITE entry PS50994]

Integrase catalytic domain profile





Description

The retroviral integrase is the enzyme responsible for the insertion of a DNA copy of the viral genome into host DNA, an essential step in the replication cycle of viruses [1]. Integrases comprise three functional and structural domains: the central core domain, which contains the catalytic residues, an N-terminal zinc finger (see <PDOC50876>) and a C-terminal DNA binding domain (see <PDOC51027>)[2].

The integrase catalytic domain catalyzes a series of reactions to integrate the viral genome into a host chromosome. In the first step, it removes two 3' end nucleotides from each strand of the linear viral DNA, leaving overhanging CA-OH ends. In the second step, the processed 3' ends are covalently joined to the 5' ends of the target DNA. In the third step, which probably involves additional cellular enzymes, unpaired nucleotides at the viral 5' ends are removed and the ends are joined to the target site 3' ends, generating an integrated provirus flanked by five base-pair direct repeats of the target site DNA [3].

The crystal structure of the catalytic domain shows a dimeric structure, with each monomer containing a five-stranded β-sheet and six α-helices (see <PDB:1ITG>) [4]. This fold is characteristic of the polynucleotidyltransferase superfamily whose members include RNase H (see <PDOC50879>), the bacteriophage Mu transposase, and the E. coli Holliday junction resolving enzyme, RuvC [5]. The catalytic domain of integrase contains the DD35E triad motif. As in other DNA-binding proteins containing this motif, these acidic residues coordinate a divalent Mg2+ in the resting enzyme. Substituting any one of these residues abolishes both processing and integration activities of integrase.

The integrase catalytic domain is also found in various transposase proteins.

The profile we developed covers the whole integrase catalytic domain.

Last update:

October 2004 / First entry.

-------------------------------------------------------------------------------

Technical section

PROSITE method (with tools and information) covered by this documentation:

INTEGRASE, PS50994; Integrase catalytic domain profile  (MATRIX)


References

1AuthorsFrankel A.D. Young J.A.
TitleHIV-1: fifteen proteins and an RNA.
SourceAnnu. Rev. Biochem. 67:1-25(1998).
PubMed ID9759480
DOI10.1146/annurev.biochem.67.1.1

2AuthorsEsposito D. Craigie R.
TitleHIV integrase structure and function.
SourceAdv. Virus. Res. 52:319-333(1999).
PubMed ID10384240

3AuthorsKatz R.A. Skalka A.M.
TitleThe retroviral enzymes.
SourceAnnu. Rev. Biochem. 63:133-173(1994).
PubMed ID7526778
DOI10.1146/annurev.bi.63.070194.001025

4AuthorsDyda F. Hickman A.B. Jenkins T.M. Engelman A. Craigie R. Davies D.R.
TitleCrystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases.
SourceScience 266:1981-1986(1994).
PubMed ID7801124

5AuthorsRice P. Craigie R. Davies D.R.
TitleRetroviral integrases and their cousins.
SourceCurr. Opin. Struct. Biol. 6:76-83(1996).
PubMed ID8696976



PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)