1oe0
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CRYSTAL STRUCTURE OF DROSOPHILA DEOXYRIBONUCLEOSIDE KINASE IN COMPLEX WITH DTTP
OverviewOverview
Deoxyribonucleoside kinases are feedback inhibited by the final products, of the salvage pathway, the deoxyribonucleoside triphosphates. In the, present study, the mechanism of feedback inhibition is presented based on, the crystal structure of a complex between the fruit fly, deoxyribonucleoside kinase and its feedback inhibitor deoxythymidine, triphosphate. The inhibitor was found to be bound as a bisubstrate, inhibitor with its nucleoside part in the nucleoside binding site and with, its phosphate groups partially occupying the phosphate donor site. The, overall structure of the enzyme--inhibitor complex is very similar to the, enzyme--substrate complexes with deoxythymidine and deoxycytidine, except, for a conformational change within a region otherwise directly involved in, catalysis. This conformational change involves a magnesium ion, which is, coordinated in the inhibitor complex to the phosphates and to the primary, base, Glu52, that normally is positioned close to the 5'-OH of the, substrate deoxyribose.
About this StructureAbout this Structure
1OE0 is a Single protein structure of sequence from Drosophila melanogaster with MG and TTP as ligands. Active as Deoxynucleoside kinase, with EC number 2.7.1.145 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for feedback inhibition of the deoxyribonucleoside salvage pathway: studies of the Drosophila deoxyribonucleoside kinase., Mikkelsen NE, Johansson K, Karlsson A, Knecht W, Andersen G, Piskur J, Munch-Petersen B, Eklund H, Biochemistry. 2003 May 20;42(19):5706-12. PMID:12741827
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