Vaccinia virus DNA topoisomerase: a model eukaryotic type IB enzyme.
Vaccinia topoisomerase has proven to be an instructive model system for mechanistic studies of the type IB family of DNA topoisomerases. The catalytically relevant functional groups at the active site and the circumferential topoisomerase-DNA interface were correctly surmised by mutational and footprint analysis of vaccinia topoisomerase in advance of structure determinations by X-ray crystallography. It is now evident from multiple crystal structures that the catalytic domains of type IB topoisomerases and site specific recombinases derive from a common ancestral strand transferase capable of forming a DNA-(3'-phosphotyrosyl)-enzyme intermediate. A constellation of conserved amino acids catalyzes attack of the tyrosine nucleophile on the scissile phosphate. Domain dynamics and DNA-induced conformational changes within the catalytic domain are likely to play a role in triggering strand scission and coordinating the strand exchange or strand passage steps.
Shuman
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Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10021, USA.
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D004254:DNA Nucleotidyltransferases / Q000737:chemistry; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry; D019426:Integrases; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D045522:Recombinases; D017386:Sequence Homology, Amino Acid; D014616:Vaccinia virus / Q000201:enzymology*; D014764:Viral Proteins / Q000737:chemistry
D004268:DNA-Binding Proteins; D045522:Recombinases; D014764:Viral Proteins; D004254:DNA Nucleotidyltransferases; D019426:Integrases; C115006:integron integrase IntI1; D004264:DNA Topoisomerases, Type I