DMCA
Atomic resolution structures of the core domain of avian sarcoma virus integrase and its D64N mutant (1999)
| Venue: | Biochemistry |
| Citations: | 6 - 2 self |
BibTeX
@ARTICLE{Lubkowski99atomicresolution,
author = {Jacek Lubkowski and Zbigniew Dauter and Fan Yang and Jerry Alex and George Merkel and Anna Marie Skalka and Alexander Wlodawer},
title = {Atomic resolution structures of the core domain of avian sarcoma virus integrase and its D64N mutant},
journal = {Biochemistry},
year = {1999},
pages = {13512--13522}
}
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Abstract
ABSTRACT: Six crystal structures of the core domain of integrase (IN) from avian sarcoma virus (ASV) and its active-site derivative containing an Asp64 f Asn substitution have been solved at atomic resolution ranging 1.02-1.42 Å. The high-quality data provide new structural information about the active site of the enzyme and clarify previous inconsistencies in the description of this fragment. The very high resolution of the data and excellent quality of the refined models explain the dynamic properties of IN and the multiple conformations of its disordered residues. They also allow an accurate description of the solvent structure and help to locate other molecules bound to the enzyme. A detailed analysis of the flexible active-site region, in particular the loop formed by residues 144-154, suggests conformational changes which may be associated with substrate binding and enzymatic activity. The pH-dependent conformational changes of the active-site loop correlates with the pH vs activity profile observed for ASV IN. Retroviruses, such as human immunodeficiency virus type 1 (HIV-1)1 or avian sarcoma virus (ASV), encode in their genes three essential enzymes: reverse transcriptase (RT), protease (PR), and integrase (IN) (1). In rare cases a retrovirus such as feline immunodeficiency virus and equine
Keyphrases
core domain atomic resolution structure d64n mutant avian sarcoma virus integrase avian sarcoma virus active site excellent quality new structural information multiple conformation flexible active-site region disordered residue reverse transcriptase enzymatic activity ph v activity profile ph-dependent conformational change atomic resolution active-site loop correlate conformational change asp64 asn substitution high-quality data six crystal structure dynamic property accurate description refined model high resolution solvent structure substrate binding rare case detailed analysis essential enzyme feline immunodeficiency virus human immunodeficiency virus type previous inconsistency
