The C-terminal regulatory domain is required for catalysis by Neisseria meningitidis alpha-isopropylmalate synthase

Biochemical and Biophysical Research Communications
Frances H A HuismanEmily J Parker

Abstract

alpha-Isopropylmalate synthase (alpha-IPMS) catalyses the first committed step in leucine biosynthesis in many pathogenic bacteria, including Neisseria meningitidis. This enzyme (NmeIPMS) has been purified, characterised, and compared to alpha-IPMS proteins from other bacteria. NmeIPMS is a homodimer which catalyses the condensation of alpha-ketoisovalerate (alpha-KIV) and acetyl coenzyme A (AcCoA), and is inhibited by leucine. NmeIPMS can use alternate alpha-ketoacids as substrates and, in contrast to alpha-IPMS from other sources, is activated by a range of metal ions including Cd(2+) and Zn(2+) that have previously been reported as inhibitory, since they suppress the dithiodipyridone assay system rather than the enzyme itself. Previous studies indicate that alpha-IPMS is a TIM barrel enzyme with an allosteric leucine-binding domain. To assess the importance of this domain, a truncated form of NmeIPMS was generated and characterised. Loss of the regulatory domain resulted in a loss of the ability to catalyse the aldol reaction, although the enzyme was still able to slowly hydrolyse AcCoA independently of alpha-KIV at a rate similar to that of the WT enzyme. This implies that the regulatory domain is not only required for cont...Continue Reading

References

Jan 1, 1988·Methods in Enzymology·G B Kohlhaw
May 1, 1996·Infection and Immunity·F C BangeW R Jacobs
Mar 10, 1999·Molecular & General Genetics : MGG·D CavalieriC Barberio
May 24, 2003·Proceedings of the National Academy of Sciences of the United States of America·Babu A ManjasettyAlice Vrielink
May 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nayden KoonEdward N Baker
May 26, 2005·Protein Expression and Purification·F William Studier
Jul 14, 2005·Journal of the American Chemical Society·Luiz P S de CarvalhoJohn S Blanchard
Jul 19, 2006·Biochemistry·Luiz Pedro S de Carvalho, John S Blanchard
Dec 10, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kechun ZhangJames C Liao

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Citations

Jul 27, 2010·PloS One·Erica M Larson, Alexander Idnurm

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