Mechanistic implications and family relationships from the structure of dethiobiotin synthetase.

摘要: Abstract Background: Biotin is the vitamin essential for many biological carboxylation reactions, such as conversion of acetyl-coenzyme A (CoA) to malonyl-CoA in fatty acid biosynthesis. Dethiobiotin synthetase (DTBS) facilitates penultimate, ureido ring closure biotin syn thesis, which a non-biotin-dependent carboxylation. DTBS displays no sequence similarity any other protein database. Structural studies provide molecular insight into reaction mechanism DTBS. Results We present structure refined 1.80 resolution with an R-factor 17.2% all terms plus unrefined data on binding substrate, 7,8-diaminopelargonic and product, dethio biotin. These confirm that forms homodimer each subunit folded single globular α / β domain. The presence sulphate ions crystals comparisons related Ha- ras -p21 oncogene product are used infer ATP-binding site, corroborated by difference electron density ATP analogue AMP-PNP. Conclusion This study establishes enzyme active site situated at dimer interface, substrate one monomer other. overall fold closely resembles three enzymes, adenylosuccinate (purA), -p21, nitrogenase iron protein, unrelated or function, indicating member diverse family enzymes.