{PDOC50994}
{PS50994; INTEGRASE}
{BEGIN}
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* Integrase catalytic domain profile *
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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 beta-sheet and six alpha-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: October 2004 / First entry.

[ 1] Frankel A.D., Young J.A.
     "HIV-1: fifteen proteins and an RNA."
     Annu. Rev. Biochem. 67:1-25(1998).
     PubMed=9759480; DOI=10.1146/annurev.biochem.67.1.1
[ 2] Esposito D., Craigie R.
     "HIV integrase structure and function."
     Adv. Virus. Res. 52:319-333(1999).
     PubMed=10384240
[ 3] Katz R.A., Skalka A.M.
     "The retroviral enzymes."
     Annu. Rev. Biochem. 63:133-173(1994).
     PubMed=7526778; DOI=10.1146/annurev.bi.63.070194.001025
[ 4] Dyda F., Hickman A.B., Jenkins T.M., Engelman A., Craigie R.,
     Davies D.R.
     "Crystal structure of the catalytic domain of HIV-1 integrase:
     similarity to other polynucleotidyl transferases."
     Science 266:1981-1986(1994).
     PubMed=7801124
[ 5] Rice P., Craigie R., Davies D.R.
     "Retroviral integrases and their cousins."
     Curr. Opin. Struct. Biol. 6:76-83(1996).
     PubMed=8696976

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