Crystal structures of the catalytic domain of HIV-1 integrase free and complexed with its metal cofactor: high level of similarity of the active site with other viral integrases.
Human immunodeficiency virus (HIV) integrase is the enzyme responsible for insertion of a DNA copy of the viral genome into host DNA, an essential step in the replication cycle of HIV. HIV-1 integrase comprises three functional and structural domains: an N-terminal zinc-binding domain, a catalytic core domain and a C-terminal DNA-binding domain. The catalytic core domain with the F185H mutation has been crystallized without sodium cacodylate in a new crystal form, free and complexed with the catalytic metal Mg2+. The structures have been determined and refined to about 2.2 A. Unlike the previously reported structures, the three active-site carboxylate residues (D,D-35-E motif) are well ordered and both aspartate residues delineate a proper metal-binding site. Comparison of the active binding site of this domain with that of other members from the polynucleotidyl transferases superfamily shows a high level of similarity, providing a confident template for the design of antiviral agents.
Maignan
S
S
Rhône-Poulenc Rorer, 13, Quai J. Guesde, Vitry/Seine, F-94403, France.
Guilloteau
J P
JP
Zhou-Liu
Q
Q
Clément-Mella
C
C
Mikol
V
V
D001665:Binding Sites; D002101:Cacodylic Acid / Q000378:metabolism; D002384:Catalysis; D018360:Crystallography, X-Ray; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry* / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure; D017434:Protein Structure, Tertiary
D002101:Cacodylic Acid; D019427:HIV Integrase; D008274:Magnesium