2v54 | pdb_00002v54

CRYSTAL STRUCTURE OF VACCINIA VIRUS THYMIDYLATE KINASE BOUND TO TDP

spinqualitylabelsall models 2v54, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2v54 is a 2 chain structure with sequence from Vaccinia virus copenhagen. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, POP, TYD Related: 2w0s Activity: dTMP kinase, with EC number 2.7.4.9 Resources: FirstGlance, OCA, RCSB, PDBsum Function [KTHY_VACCC] Poxvirus TMP kinase is able to phosphorylate dTMP, dUMP and also dGMP from any purine and pyrimidine nucleoside triphosphate. The large substrate specificity is explained by the presence of a canal connecting the edge of the dimer interface to the TMP base binding pocket, canal not found in the human homolog (By similarity). 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 PubMed Unlike most DNA viruses, poxviruses replicate in the cytoplasm of host cells. They encode enzymes needed for genome replication and transcription, including their own thymidine and thymidylate kinases. Some herpes viruses encode only 1 enzyme catalyzing both reactions, a peculiarity used for prodrug activation to obtain maximum specificity. We have solved the crystal structures of vaccinia virus thymidylate kinase bound to TDP or brivudin monophosphate. Although the viral and human enzymes have similar sequences (42% identity), they differ in their homodimeric association and active-site geometry. The vaccinia TMP kinase dimer arrangement is orthogonal and not antiparallel as in human enzyme. This different monomer orientation is related to the presence of a canal connecting the edge of the dimer interface to the TMP base binding pocket. Consequently, the pox enzyme accommodates nucleotides with bulkier bases, like brivudin monophosphate and dGMP; these are efficiently phosphorylated and stabilize the enzyme. The brivudin monophosphate-bound structure explains the structural basis for this specificity, opening the way to the rational development of specific antipox agents that may also be suitable for poxvirus TMP kinase gene-based chemotherapy of cancer. Crystal structure of poxvirus thymidylate kinase: an unexpected dimerization has implications for antiviral therapy.,Caillat C, Topalis D, Agrofoglio LA, Pochet S, Balzarini J, Deville-Bonne D, Meyer P Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16900-5. Epub 2008 Oct 29. PMID:18971333 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thymidylate kinase

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