Three‐dimensional structural resemblance between the ribonuclease H and connection domains of HIV reverse transcriptase and the ATPase fold revealed using graph theoretical techniques

FEBS Letters

Kumar, Kiran¹  Rice, David W.¹  Artymiuk, Peter J.¹  Willett, Peter²  Grindley, Helen M.² 

[1] Krebs Institute, Departments of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK;Information Studies, University of Sheffield, Sheffield, S10 2TN, UK

关键词: Structural similarity;    Graph theory;    HIV;    AIDS;    Reverse transcriptase;    Ribonuclease H;    ATPase fold;    RT;    reverse transcriptase;    RNase;    ribonuclease;    HIV;    human immunodefiency virus;    AIDS;    acquired immune deficiency syndrome;    PDB;    Protein Data Bank (Brookhaven);    3D;    three-dimensional;    SSE;    secondary structure element;   

DOI  :  10.1016/0014-5793(93)81523-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown