2no6 | pdb_00002no6

C4S dCK variant of dCK in complex with FTC+ADP

spinqualitylabelsall models 2no6, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2no6 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, ETV Related: 1p5z, 1p60, 1p61, 1p62, 2a2z, 2a30, 2no0, 2no1, 1no7, 2no9, 2noa Gene: DCK (HUMAN) Activity: Deoxycytidine kinase, with EC number 2.7.1.74 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DCK_HUMAN] Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents. 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 Biological molecules are predominantly enantioselective. Yet currently two nucleoside analogue prodrugs (3TC and FTC) with opposite chirality compared to physiological nucleosides are clinically approved for the treatment of HIV infections. These prodrugs require conversion to their triphosphorylated forms to achieve pharmacological activity. The first step in the activation of these agents is catalyzed by human deoxycytidine kinase (dCK). This enzyme possesses the ability to phosphorylate nucleosides of the unnatural l-chirality. To understand the molecular basis for the nonenantioselectivity of dCK, we solved the crystal structures of the enzyme in complex with the l-enantiomer and of its physiological substrate deoxycytidine and with the l-nucleoside analogue FTC. These were compared to a structure solved with d-dC. Our results highlight structural adjustments imposed on the l-nucleosides and properties of the enzyme endowing it with the ability to phosphorylate substrates with nonphysiological chirality. This work reveals the molecular basis for the activation of l-nucleosides by dCK. Nonenantioselectivity Property of Human Deoxycytidine Kinase Explained by Structures of the Enzyme in Complex with l- and d-Nucleosides.,Sabini E, Hazra S, Konrad M, Lavie A J Med Chem. 2007 Jun 28;50(13):3004-14. Epub 2007 May 27. PMID:17530837 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Deoxycytidine kinase

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