Atomic Resolution Structures of the Core Domain of Avian Sarcoma Virus Integrase and Its D64N Mutant
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- 作者：Jacek Lubkowski ; Zbigniew Dauter ; Fan Yang ; Jerry Alexandratos ; George Merkel ; Anna Marie Skalka ; and Alexander Wlodawer
- 刊名：Biochemistry
- 出版年：1999
- 出版时间：October 12, 1999
- 年：1999
- 卷：38
- 期：41
- 页码：13512 - 13522
- 全文大小：551K
- 年卷期：v.38,no.41(October 12, 1999)
- ISSN：1520-4995
文摘
Six crystal structures of the core domain of integrase (IN) from avian sarcoma virus (ASV)and its active-site derivative containing an Asp64 
Asn substitution have been solved at atomic resolutionranging 1.02-1.42 Å. The high-quality data provide new structural information about the active site ofthe enzyme and clarify previous inconsistencies in the description of this fragment. The very high resolutionof the data and excellent quality of the refined models explain the dynamic properties of IN and themultiple conformations of its disordered residues. They also allow an accurate description of the solventstructure and help to locate other molecules bound to the enzyme. A detailed analysis of the flexibleactive-site region, in particular the loop formed by residues 144-154, suggests conformational changeswhich may be associated with substrate binding and enzymatic activity. The pH-dependent conformationalchanges of the active-site loop correlates with the pH vs activity profile observed for ASV IN.
Asn substitution have been solved at atomic resolutionranging 1.02-1.42 Å. The high-quality data provide new structural information about the active site ofthe enzyme and clarify previous inconsistencies in the description of this fragment. The very high resolutionof the data and excellent quality of the refined models explain the dynamic properties of IN and themultiple conformations of its disordered residues. They also allow an accurate description of the solventstructure and help to locate other molecules bound to the enzyme. A detailed analysis of the flexibleactive-site region, in particular the loop formed by residues 144-154, suggests conformational changeswhich may be associated with substrate binding and enzymatic activity. The pH-dependent conformationalchanges of the active-site loop correlates with the pH vs activity profile observed for ASV IN.