Three-dimensional structural resemblance between the ribonuclease H and connection domains of HIV reverse transcriptase and the ATPase fold revealed using graph theoretical techniques.
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.
Artymiuk
P J
PJ
Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, UK.
Grindley
H M
HM
Kumar
K
K
Rice
D W
DW
Willett
P
P
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
D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D016914:Ribonuclease H; D000251:Adenosine Triphosphatases