The Simple and Unique Allosteric Machinery of Thermus caldophilus Lactate Dehydrogenase : Structure-Function Relationship in Bacterial Allosteric LDHs.
Many bacterial L-lactate dehydrogenases (LDH) are allosteric enzymes, and usually activated by fructose 1,6-bisphosphate (FBP) and often also by substrate pyruvate. The active and inactive state structures demonstrate that Thermus caldophilus, Lactobacillus casei, and Bifidobacterium longum LDHs consistently undergo allosteric transition according to Monod-Wyman-Changeux model, where the active (R) and inactive (T) states of the enzymes coexist in an allosteric equilibrium (pre-existing equilibrium) independently of allosteric effectors. The three enzymes consistently take on open and closed conformations of the homotetramers for the T and R states, coupling the quaternary structural changes with the structural changes in binding sites for substrate and FBP though tertiary structural changes. Nevertheless, the three enzymes undergo markedly different structural changes from one another, indicating that there is a high variety in the allosteric machineries of bacterial LDHs. L. casei LDH undergoes the largest quaternary structural change in the three enzymes, and regulates its catalytic activity though a large linkage frame for allosteric motion. In contrast, T. caldophilus LDH exhibits the simplest allosteric motion in the three enzymes, involving a simple mobile structural core for the allosteric motion. TcLDH likely mediates its allosteric equilibrium mostly through electrostatic repulsion within the protein molecule, providing an insight for regulation machineries in bacterial allosteric LDHs.
Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. htaguchi@rs.noda.tus.ac.jp.
Hayao
H
Taguchi
D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000069978:Bifidobacterium longum / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D001665:Binding Sites; D005635:Fructosediphosphates / Q000737:chemistry* / Q000378:metabolism; D015870:Gene Expression; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007780:Lacticaseibacillus casei / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019289:Pyruvic Acid / Q000737:chemistry* / Q000378:metabolism; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013824:Thermus / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics
D001426:Bacterial Proteins; D005635:Fructosediphosphates; D021122:Protein Subunits; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; C029063:fructose-1,6-diphosphate
Allostery; L-Lactate dehydrogenase; Lactic bacteria; Monod-Wyman-Changeux model; Pre-existence equilibrium; Thermophilic bacteria