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From Proteopedia
Crystal Structure of AAV2 Rep40-ADP complex
Structural highlights
FunctionREP68_AAV2S Plays an essential role in the initiation of viral DNA synthesis. Binds specifically to an inverted terminal repeat element (ITR) on the 3' and 5' ends of the viral DNA, where it cleaves a site specifically to generate a priming site for initiation of the synthesis of a complementary strand. Plays also a role as transcriptional regulator, DNA helicase and as key factor in site-specific integration of the viral genome. Inhibits the host cell cycle G1/S and G2/M transitions. These arrests may provide essential cellular factors for viral DNA replication.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe have determined the structure of adeno-associated virus type 2 (AAV2) Rep40 to 2.1-A resolution with ADP bound at the active site. The complex crystallizes as a monomer with one ADP molecule positioned in an unexpectedly open binding site. The nucleotide-binding pocket consists of the P-loop residues interacting with the phosphates and a loop (nucleoside-binding loop) that emanates from the last strand of the central beta-sheet and interacts with the sugar and base. As a result of the open nature of the binding site, one face of the adenine ring is completely exposed to the solvent, and consequently the number of protein-nucleotide contacts is scarce as compared with other P-loop nucleotide phosphohydrolases. The conformation of the ADP molecule in its binding site bears a resemblance to those found in only three other families of P-loop ATPases: the ATP-binding cassette transporter family, the bacterial RecA proteins, and the type II topoisomerase family. In all these cases, oligomerization is required to attain a competent nucleotide-binding pocket. We propose that this characteristic is native to superfamily 3 helicases and allows for an additional mechanism of regulation by these multifunctional proteins. Furthermore, it explains the strong tendency by members of this family such as simian virus 40 TAg to oligomerize after binding ATP. Structure of adeno-associated virus type 2 Rep40-ADP complex: insight into nucleotide recognition and catalysis by superfamily 3 helicases.,James JA, Aggarwal AK, Linden RM, Escalante CR Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12455-60. Epub 2004 Aug 13. PMID:15310852[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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