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8AB3

Crystal Structure of the Lactate Dehydrogenase of Cyanobacterium Aponinum in complex with oxamate, NADH and FBP.

Summary for 8AB3
Entry DOI10.2210/pdb8ab3/pdb
Related8AB2
DescriptorL-lactate dehydrogenase, OXAMIC ACID, 1,6-di-O-phosphono-beta-D-fructofuranose, ... (5 entities in total)
Functional Keywordsallostery, lactate dehydrogenase, crystallophore / xo4, oxidoreductase
Biological sourceCyanobacterium aponinum
Total number of polymer chains4
Total formula weight151840.99
Authors
Robin, A.Y.,Girard, E.,Madern, D. (deposition date: 2022-07-04, release date: 2022-07-27, Last modification date: 2024-02-07)
Primary citationRobin, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.616 Å)
Structure validation

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건을2024-11-06부터공개중

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