Slow-onset feedback inhibition: Inhibition of Mycobacterium tuberculosis α-isopropylmalate synthase by L-leucine

Luiz P S De Carvalho, Argyrides Argyrou, John S. Blanchard

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

This report describes the first demonstration of slow-onset feedback inhibition of an enzyme that catalyzes the first committed step in a biosynthetic pathway. α-Isopropylmalate synthase (IPMS) catalyzes the first committed step of the l-leucine biosynthetic pathway and is feedback-inhibited by l-leucine. Initial velocity experiments on the Mycobacterium tuberculosis IPMS indicate that inhibition by l-leucine is linearly noncompetitive versus α-ketoisovalerate. Time-courses displayed a burst of product formation followed by a linear steady-state rate when reactions were initiated by the addition of enzyme. The burst rate showed a hyperbolic dependence on the concentration of l-leucine indicating that inhibition proceeds in two steps, an initial rapid binding step followed by slow isomerization to a more tightly bound complex.

Original languageEnglish (US)
Pages (from-to)10004-10005
Number of pages2
JournalJournal of the American Chemical Society
Volume127
Issue number28
DOIs
StatePublished - Jul 20 2005

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Mycobacterium tuberculosis
Leucine
Enzymes
Feedback
Enzyme inhibition
Biosynthetic Pathways
Isomerization
Reaction rates
Demonstrations
Experiments

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Slow-onset feedback inhibition : Inhibition of Mycobacterium tuberculosis α-isopropylmalate synthase by L-leucine. / De Carvalho, Luiz P S; Argyrou, Argyrides; Blanchard, John S.

In: Journal of the American Chemical Society, Vol. 127, No. 28, 20.07.2005, p. 10004-10005.

Research output: Contribution to journalArticle

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