title: Three-dimensional structural resemblance between the ribonuclease H and connection domains of HIV reverse transcriptase and the ATPase fold revealed using graph theoretical techniques.
abstract: Using 3D searching techniques based on algorithms derived from graph theory, we have established two previously unreported structural similarities involving the ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT). First, we report that there is a strong similarity between the 3D folds of the RNase H domain of RT and the 'ATPase folds' of hexokinase, the 70 kDa heat-shock cognate protein and actin. Like RNase H, these enzymes are involved in nucleotide binding and metal ion-catalysed cleavage of a phosphodiester bond. Similarities of the folding motif and the position of the metal-binding site in these enzymes suggest possible functional analogies and evolutionary relationships with RNase H. Second, we find there is a strong resemblance between the folds of the RNase H domain and of the p66 and p51 'connection' domains of RT. It is possible that this striking similarity within the RT structure indicates a possible ancestral gene doubling event. The similarity may also indicate that the connection domains possess functional roles in addition to those previously suggested, and they may therefore represent a further target for the design of therapeutic agents.
authors.affiliation: Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Artymiuk
authors.forename: H M
authors.initials: HM
authors.lastname: Grindley
authors.forename: K
authors.initials: K
authors.lastname: Kumar
authors.forename: D W
authors.initials: DW
authors.lastname: Rice
authors.forename: P
authors.initials: P
authors.lastname: Willett
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D006678:HIV / Q000201:enzymology*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology*; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry* / Q000378:metabolism; D016914:Ribonuclease H / Q000737:chemistry* / Q000378:metabolism; D012984:Software
chemical_list: D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D016914:Ribonuclease H; D000251:Adenosine Triphosphatases