title: V-type allosteric inhibition is described by a shift in the rate-determining step for α-isopropylmalate synthase from Mycobacterium tuberculosis.
abstract: The kinetic parameters affected by allosteric mechanisms contain collections of rate constants that vary based on differences in the relative rates of individual steps in the reaction. Thus, it may not be useful to compare enzymes with similar allosteric mechanisms unless the point of regulation has been identified. Rapid reaction kinetics and kinetic isotope effects provide a detailed description of V-type feedback allosteric inhibition in α-isopropylmalate synthase from Mycobacterium tuberculosis, an evolutionarily conserved model allosteric system. Results are consistent with a shift in the rate-determining step from product release to the hydrolytic step in catalysis in the presence of the effector.
authors.affiliation: Department of Chemistry, The University of Alabama , Tuscaloosa, Alabama 35487, United States.
authors.forename: Ashley K
authors.initials: AK
authors.lastname: Casey
authors.forename: Erica L
authors.initials: EL
authors.lastname: Schwalm
authors.forename: Brittani N
authors.initials: BN
authors.lastname: Hays
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Frantom
mesh_terms: D015079:2-Isopropylmalate Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000494:Allosteric Regulation / Q000187:drug effects*; D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology*; D055162:Biocatalysis; D007700:Kinetics; D007930:Leucine / Q000096:biosynthesis / Q000737:chemistry; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D015079:2-Isopropylmalate Synthase; D007930:Leucine