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Forskningsartikel2003Vetenskapligt granskad

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


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

Publicerad i

2003, Volym: 42, nummer: 19, sidor: 5706-5712

      SLU författare

      • Mikkelsen, Nils

        • Institutionen för molekylärbiologi, Sveriges lantbruksuniversitet
        • Eklund, Hans

          • Institutionen för molekylärbiologi, Sveriges lantbruksuniversitet

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        Förnyelsebar bioenergi

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