Modifying the determinants of α-ketoacid substrate selectivity in mycobacterium tuberculosis α-isopropylmalate synthase.
FEBS Lett
; 588(9): 1603-7, 2014 May 02.
Article
em En
| MEDLINE
| ID: mdl-24613923
ABSTRACT
α-Isopropylmalate synthase (IPMS) catalyses the reaction between α-ketoisovalerate and acetyl coenzyme A (AcCoA) in the first step of leucine biosynthesis. IPMS is closely related to homocitrate synthase, which catalyses the reaction between AcCoA and the unbranched α-ketoacid α-ketoglutarate. Analysis of these enzymes suggests that several differently conserved key residues are responsible for the different substrate selectivity. These residues were systematically substituted in the Mycobacterium tuberculosis IPMS, resulting in changes in substrate specificity. A variant of IPMS was constructed with a preference for the unbranched α-ketoacids α-ketobutyrate and pyruvate over the natural branched substrate α-ketoisovalerate.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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2-Isopropilmalato Sintase
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Mycobacterium tuberculosis
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article