1asu

Categories: Avian sarcoma virus | Single protein | Alexandratos, J. | Bujacz, G. | Jaskolski, M. | Wlodawer, A. | EPE | Dna integration

AVIAN SARCOMA VIRUS INTEGRASE CATALYTIC CORE DOMAIN CRYSTALLIZED FROM 2% PEG 400, 2M AMMONIUM SULFATE, HEPES PH 7.5

Overview

Retroviral integrase (IN) functions to insert retroviral DNA into the host cell chromosome in a highly coordinated manner. IN catalyzes two biochemically separable reactions: processing of the viral DNA ends and joining of these ends to the host DNA. Previous studies suggested that these two reactions are chemically similar and are carried out by a single active site that is characterized by a highly conserved constellation of carboxylate residues, the D,D(35)E motif. We report here the crystal structure of the isolated catalytic domain of avian sarcoma virus (ASV) IN, solved using multiwavelength anomalous diffraction data for a selenomethionine derivative and refined at 1.7 A resolution. The protein is a crystallographic dimer with each monomer featuring a five-stranded mixed beta-sheet region surrounded by five alpha-helices. Based on the general fold and the arrangement of catalytic carboxylate residues, it is apparent that ASV IN is a member of a superfamily of proteins that also includes two types of nucleases, RuvC and RNase H. The general fold and the dimer interface are similar to those of the analogous domain of HIV-1 IN, whose crystal structure has been determined at 2.5 A resolution. However, the ASV IN structure is more complete in that all three critical carboxylic acids, Asp64, Asp121 and Glu157, are ordered. The ordered active site and the considerably higher resolution of the present structure are all important to an understanding of the mechanism of retroviral DNA integration, as well as for designing antiviral agents that may be effective against HIV.

About this Structure

1ASU is a Single protein structure of sequence from Avian sarcoma virus with as ligand. Full crystallographic information is available from OCA.

Reference

High-resolution structure of the catalytic domain of avian sarcoma virus integrase., Bujacz G, Jaskolski M, Alexandratos J, Wlodawer A, Merkel G, Katz RA, Skalka AM, J Mol Biol. 1995 Oct 20;253(2):333-46. PMID:7563093

Page seeded by OCA on Thu Feb 21 11:47:56 2008