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Rational design of an inhibitor of dethiobiotin synthetase; interaction of 6-hydroxypyrimindin-4(3H)-one with the adenine base binding site |
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| Authors: | Dmitriy Alexeev Robert L Baxter Dominic J Campopiano Robin S McAlpine Lisa McIver Lindsay Sawyer |
| Institution: | a Edinburgh Centre for Protein Technology, The Joseph Black Chemistry Building, The University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK b Structural Biochemistry Group, The University of Edinburgh, Swann Building, Mayfield Road, Edinburgh EH9 3JR, UK. |
| Abstract: | Modelling of the H-bonding interactions involved in the binding of the adenine base component of ATP to E. coli dethiobiotin synthetase (DTBS) suggested that 6-hydroxypyrimidin-4(3H)-one (6-HP4) should selectively bind to this site in the enzyme. Kinetic studies show that 6-HP4 is a competitive inhibitor of DTBS and x-ray crystallography shows that 6-HP4 binds specifically in the purine base binding site of the enzyme. |
| Keywords: | ATP binding site enzyme inhibitor nucleotide-protein interaction inhibitor design dethiobiotin synthetase biotin biosynthesis |
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