Avtor/Urednik		Mikkelsen, Nils Egil; Johansson, Kenth; Karlsson, Andreas; Knecht, Wolfgang; Andersen, Gorm; Piškur, Jure; Munch-Petersen, Birgitte; Eklund, Hans
Naslov		Structural basis for feedback inhibition of the deoxyribonucleoside salvage pathway: studies of the Drosophila deoxyribonucleoside kinase
Tip		članek
Vir		Biochemistry
Vol. in št.		Letnik 42, št. 19
Leto izdaje		2003
Obseg		str. 5706-12
Jezik		eng
Abstrakt		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.
Deskriptorji		ADENOSINE TRIPHOSPHATE ANIMALS BINDING SITES CRYSTALLOGRAPHY, X-RAY DEOXYRIBONUCLEOSIDES DROSOPHILA MELANOGASTER FEEDBACK KINETICS MODELS, MOLECULAR PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR) PROTEIN CONFORMATION RECOMBINANT PROTEINS THYMINE NUCLEOTIDES