2ocp
From Proteopedia
Crystal Structure of Human Deoxyguanosine Kinase
Structural highlights
DiseaseDGUOK_HUMAN Defects in DGUOK are the cause of mitochondrial DNA depletion syndrome type 3 (MTDPS3) [MIM:251880. A disorder characterized by onset in infancy of progressive liver failure, hypoglycemia, increased lactate in body fluids, and neurologic abnormalities including hypotonia, encephalopathy, peripheral neuropathy. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes and mtDNA depletion.[1] [2] FunctionDGUOK_HUMAN Required for the phosphorylation of several deoxyribonucleosides and certain nucleoside analogs widely employed as antiviral and chemotherapeutic agents.[3] 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 PubMedDeoxyribonucleoside kinases phosphorylate deoxyribonucleosides and activate a number of medically important nucleoside analogs. Here we report the structure of the Drosophila deoxyribonucleoside kinase with deoxycytidine bound at the nucleoside binding site and that of the human deoxyguanosine kinase with ATP at the nucleoside substrate binding site. Compared to the human kinase, the Drosophila kinase has a wider substrate cleft, which may be responsible for the broad substrate specificity of this enzyme. The human deoxyguanosine kinase is highly specific for purine substrates; this is apparently due to the presence of Arg 118, which provides favorable hydrogen bonding interactions with the substrate. The two new structures provide an explanation for the substrate specificity of cellular deoxyribonucleoside kinases. Structural basis for substrate specificities of cellular deoxyribonucleoside kinases.,Johansson K, Ramaswamy S, Ljungcrantz C, Knecht W, Piskur J, Munch-Petersen B, Eriksson S, Eklund H Nat Struct Biol. 2001 Jul;8(7):616-20. PMID:11427893[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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