Atomic resolution structures of the core domain of avian sarcoma virus integrase and its D64N mutant

Six crystal structures of the core domain of integrase (IN) from avian sarc oma virus (ASV) and its active-site derivative containing an Asp64 --> Asn substitution have been solved at atomic resolution ranging 1.02-1.42 Angstr om. The high-quality data provide new structural information about the acti ve site of the enzyme and clarify previous inconsistencies in the descripti on of this fragment. The very high resolution of the data and excellent qua lity of the refined models explain the dynamic properties of IN and the mul tiple conformations of its disordered residues. They also allow an accurate description of the solvent structure and help to locate other molecules bo und 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 activi ty. The pH-dependent conformational changes of the active-site loop correla tes with the pH vs activity profile observed for ASV IN.