3qen | pdb_00003qen

S74E dCK in complex with 5-bromodeoxycytidine and UDP

spinqualitylabelsall models 3qen, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qen 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: 5BT, UDP Related: 3qej, 3qeo 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. Publication Abstract from PubMed Deoxycytidine kinase (dCK) uses either ATP or UTP as phosphoryl donors to catalyze the phosphorylation of nucleoside acceptors. The kinetic properties of human dCK are modulated in vivo by phosphorylation of serine 74. This residue is a part of the insert region and is situated distant to the active site. Replacing the serine with a glutamic acid (S74E variant) can mimic phosphorylation of Ser74. To understand how phosphorylation affects the catalytic properties of dCK, we examined the S74E variant of dCK both structurally and kinetically. We observe that the presence of a glutamic acid at position 74 favors the enzyme adopting the open conformation. Glu74 stabilizes the open conformation by directly interacting with the indole side chain of Trp58, a residue that is in close proximity to the base of the nucleoside substrate. The open dCK conformation is competent for the binding of nucleoside but not for phosphoryl transfer. In contrast, the closed conformation is competent for phosphoryl transfer but not for product release. Thus, dCK must transition between the open and closed states during the catalytic cycle. We propose a reaction scheme for dCK that incorporates the transition between the open and closed states, and this serves to rationalize the observed kinetic differences between wild type dCK and the S74E variant. Post-translational phosphorylation of serine 74 of human deoxycytidine kinase favors the enzyme adopting the open conformation making it competent for nucleoside binding and release.,Hazra S, Szewczak A, Ort S, Konrad M, Lavie A Biochemistry. 2011 Feb 25. PMID:21351740 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Deoxycytidine kinase 3D structures

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