1OE0

CRYSTAL STRUCTURE OF DROSOPHILA DEOXYRIBONUCLEOSIDE KINASE IN COMPLEX WITH DTTP

Summary for 1OE0

• Entry DOI: 10.2210/pdb1oe0/pdb
• Related: 1J90
• Descriptor: DEOXYRIBONUCLEOSIDE KINASE, THYMIDINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: transferase, drosophila, deoxyribonucleoside kinase, dttp, complex, feedback inhibition, salvage pathway
• Biological source: DROSOPHILA MELANOGASTER (FRUIT FLY)
• Total number of polymer chains: 4
• Total formula weight: 109652.72

Authors

Mikkelsen, N.E.,Johansson, K.,Karlsson, A.,Knecht, W.,Andersen, G.,Piskur, J.,Munch-Petersen, B.,Eklund, H. (deposition date: 2003-03-17, release date: 2003-10-23, Last modification date: 2023-12-13)

Primary citation

Mikkelsen, N.E.,Johansson, K.,Karlsson, A.,Knecht, W.,Andersen, G.,Piskur, J.,Munch-Petersen, B.,Eklund, H.
Structural Basis for Feedback Inhibition of the Deoxyribonucleoside Salvage Pathway:Studies of the Drosophila Deoxyribonucleoside Kinase
Biochemistry, 42:5706-, 2003

PubMed Abstract: 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.

PubMed: 12741827
DOI: 10.1021/BI0340043

Experimental method

X-RAY DIFFRACTION (2.4 Å)