3ipx | pdb_00003ipx
X-Ray structure of Human Deoxycytidine Kinase in complex with ADP and an inhibitor
Structural highlights
FunctionDCK_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.[1] [2] 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 PubMedA series of deoxycytidine kinase inhibitors was simultaneously optimized for potency and PK properties. A co-crystal structure then allowed merging this series with a high throughput screening hit to afford a highly potent, selective and orally bioavailable inhibitor, compound 10. This compound showed dose dependent inhibition of deoxycytidine kinase in vivo. Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors.,Jessop TC, Tarver JE, Carlsen M, Xu A, Healy JP, Heim-Riether A, Fu Q, Taylor JA, Augeri DJ, Shen M, Stouch TR, Swanson RV, Tari LW, Hunter M, Hoffman I, Keyes PE, Yu XC, Miranda M, Liu Q, Swaffield JC, David Kimball S, Nouraldeen A, Wilson AG, Foushee AM, Jhaver K, Finch R, Anderson S, Oravecz T, Carson KG Bioorg Med Chem Lett. 2009 Dec 1;19(23):6784-7. Epub 2009 Sep 25. PMID:19836232[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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