8AB2

Crystal Structure of the Lactate Dehydrogenase of Cyanobacterium Aponinum in its apo form.

8AB2 の概要

• エントリーDOI: 10.2210/pdb8ab2/pdb
• 分子名称: L-lactate dehydrogenase, Tb-Xo4, TERBIUM(III) ION, ... (5 entities in total)
• 機能のキーワード: allostery, lactate dehydrogenase, crystallophore / xo4, oxidoreductase
• 由来する生物種: Cyanobacterium aponinum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38130.90

構造登録者

Robin, A.Y.,Girard, E.,Madern, D. (登録日: 2022-07-04, 公開日: 2022-08-03, 最終更新日: 2024-02-07)

主引用文献

Robin, A.Y.,Brochier-Armanet, C.,Bertrand, Q.,Barette, C.,Girard, E.,Madern, D.
Deciphering Evolutionary Trajectories of Lactate Dehydrogenases Provides New Insights into Allostery.
Mol.Biol.Evol., 40:-, 2023

PubMed Abstract: Lactate dehydrogenase (LDH, EC.1.1.127) is an important enzyme engaged in the anaerobic metabolism of cells, catalyzing the conversion of pyruvate to lactate and NADH to NAD+. LDH is a relevant enzyme to investigate structure-function relationships. The present work provides the missing link in our understanding of the evolution of LDHs. This allows to explain (i) the various evolutionary origins of LDHs in eukaryotic cells and their further diversification and (ii) subtle phenotypic modifications with respect to their regulation capacity. We identified a group of cyanobacterial LDHs displaying eukaryotic-like LDH sequence features. The biochemical and structural characterization of Cyanobacterium aponinum LDH, taken as representative, unexpectedly revealed that it displays homotropic and heterotropic activation, typical of an allosteric enzyme, whereas it harbors a long N-terminal extension, a structural feature considered responsible for the lack of allosteric capacity in eukaryotic LDHs. Its crystallographic structure was solved in 2 different configurations typical of the R-active and T-inactive states encountered in allosteric LDHs. Structural comparisons coupled with our evolutionary analyses helped to identify 2 amino acid positions that could have had a major role in the attenuation and extinction of the allosteric activation in eukaryotic LDHs rather than the presence of the N-terminal extension. We tested this hypothesis by site-directed mutagenesis. The resulting C. aponinum LDH mutants displayed reduced allosteric capacity mimicking those encountered in plants and human LDHs. This study provides a new evolutionary scenario of LDHs that unifies descriptions of regulatory properties with structural and mutational patterns of these important enzymes.

PubMed: 37797308
DOI: 10.1093/molbev/msad223

実験手法

X-RAY DIFFRACTION (2.1 Å)