Substrate binding and carboxylation by dethiobiotin synthetase--a kinetic and X-ray study

Structure
D AlexeevL Sawyer

Abstract

The vitamin biotin is a ubiquitous prosthetic group of carboxylase and transcarboxylase enzymes. Biotin biosynthesis occurs by similar pathways in microorganisms and plants. The penultimate step in biotin biosynthesis, catalyzed by dethiobiotin synthetase (DTBS), involves a unique ATP-dependent N-carboxylation, resulting in formation of the ureido ring function of dethiobiotin. The first two steps of dethiobiotin formation, which is a complex, multistep enzymatic reaction, have been elucidated by a combination of X-ray crystallography and kinetic methods. The first step in catalysis by DTBS is the formation of an enzyme-substrate complex and the second is the enzymatic carboxylation of the bound substrate. Both steps are Mg2+ dependent. The kinetic constants in the presence and absence of Mg2+ have been measured and a set of X-ray structures determined at different stages of the reaction. The conformational changes in the active site of the enzyme, induced by Mg2+, substrate binding and substrate carboxylation, have been monitored crystallographically and are discussed. Sulfate ions bound to DTBS may mimic the behaviour of the alpha- and gamma-phosphates of ATP in Mg2+ binding and in the subsequent steps of the reaction. Mg2+ i...Continue Reading

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Citations

Dec 1, 1996·Current Opinion in Structural Biology·Y Lindqvist, G Schneider
Oct 10, 2012·Proceedings of the National Academy of Sciences of the United States of America·Vinayak AgarwalJohn E Cronan
May 20, 1998·Proceedings of the National Academy of Sciences of the United States of America·H KäckG Schneider
Apr 27, 2001·FEBS Letters·G Schneider, Y Lindqvist
Sep 10, 2002·The Journal of Biological Chemistry·Jenny SandmarkGunter Schneider

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