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The Simple and Unique Allosteric Machinery of Thermus caldophilus Lactate Dehydrogenase

Structure-Function Relationship in Bacterial Allosteric LDHs

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Protein Reviews

Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 925))

Abstract

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.

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Abbreviations

BlLDH:

Bifidobacterium longum LDH

DMLDH:

dogfish muscle LDH

FBP:

fructose 1,6-bisphosphate

GsLDH:

Geobacillus stearothermophilus LDH

LcLDH:

Lactobacillus casei LDH

LDH:

L-lactate dehydrogenase

LpLDH:

Lactobacillus pentosus LDH

RMSD:

root mean square deviation

TcLDH:

Thermus caldophilus LDH

TmLDH:

Thermotoga maritima LDH

TtLDH:

Thermus thermophilus LDH

TtMDH:

Thermus thermophilus MDH

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Acknowledgements

I am deeply grateful to Drs. Kazuhito Arai, Akimasa Miyanaga, and Masahiro Nakajima in my laboratory for many supports and discussions as to the descriptions of the structures and functions of TcLDH and LcLDH. The crystallographic studies for these two enzymes were performed with the approval of the Photon Factory Program Advisory Committee (Proposal Nos. 2004G136 and 2006G160).

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  1. Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan

    Hayao Taguchi

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  1. Hayao Taguchi
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Correspondence to Hayao Taguchi .

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  1. Biochem and Mol Biol, Baylor College of Medicine, Houston, Texas, USA

    M. Zouhair Atassi

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Taguchi, H. (2016). The Simple and Unique Allosteric Machinery of Thermus caldophilus Lactate Dehydrogenase. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 925. Springer, Singapore. https://doi.org/10.1007/5584_2016_171

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