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

被引:246
作者
Maignan, S [1 ]
Guilloteau, JP [1 ]
Zhou-Liu, Q [1 ]
Clément-Mella, C [1 ]
Mikol, V [1 ]
机构
[1] Rhone Poulenc Rorer, F-94403 Vitry, France
关键词
integrase; HIV; X-ray crystallography; protein crystallization; cacodylate;
D O I
10.1006/jmbi.1998.2002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Angstrom. 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. (C) 1998 Academic Press.
引用
收藏
页码:359 / 368
页数:10
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