To the Understanding of Catalysis by D‐Amino Acid Transaminases: A Case Study of the Enzyme from Aminobacterium colombiense

Shilova, S.A.; Khrenova, M.G.; Matyuta, I.O.; Nikolaeva, A.Y.; Rakitina, T.V.; Klyachko, N.L.; Minyaev, M.E.; Boyko, K.M.; Popov, V.O.; Bezsudnova, E.Y.

Авторы: Shilova S.A., Khrenova M.G., Matyuta I.O., Nikolaeva A.Y., Rakitina T.V., Klyachko N.L., Minyaev M.E., Boyko K.M., Popov V.O., Bezsudnova E.Y.
Журнал: Molecules
Том: 28
Год издания: 2023
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 1
Последняя страница: 22
Номер статьи: 2109
DOI: 10.3390/molecules28052109
Аннотация: Shilova, S.A.; Khrenova, M.G.; Matyuta, I.O.; Nikolaeva, A.Y.; Rakitina, T.V.; Klyachko, N.L.; Minyaev, M.E.; Boyko, K.M.; Popov, V.O.; Bezsudnova, E.Y. To the Understanding of Catalysis by D‐Amino Acid Transaminases: A Case Study of the Enzyme from Aminobacterium colombiense. Molecules 2023, 28, 2109. https://doi.org/10.3390/molecules28052109 IF 4.927 (Q1). Published online: 23.02.2023Pyridoxal‐5′‐phosphate (PLP)‐dependent transaminases are highly efficient biocatalystsfor stereoselective amination. D‐amino acid transaminases can catalyze stereoselective transamina‐tion producing optically pure D‐amino acids. The knowledge of substrate binding mode and sub‐strate differentiation mechanism in D‐amino acid transaminases comes down to the analysis of thetransaminase from Bacillus subtilis. However, at least two groups of D‐amino acid transaminasesdiffering in the active site organization are known today. Here, we present a detailed study of D‐amino acid transaminase from the gram‐negative bacterium Aminobacterium colombiense with a sub‐strate binding mode different from that for the transaminase from B. subtilis. We study the enzymeusing kinetic analysis, molecular modeling, and structural analysis of holoenzyme and its complexwith D‐glutamate. We compare the multipoint binding of D‐glutamate with the binding of othersubstrates, D‐aspartate and D‐ornithine. QM/MM MD simulation reveals that the substrate can actas a base and its proton can be transferred from the amino group to the α‐carboxylate group. Thisprocess occurs simultaneously with the nucleophilic attack of the PLP carbon atom by the nitrogenatom of the substrate forming gem‐diamine at the transimination step. This explains the absence ofthe catalytic activity toward (R)‐amines that lack an α‐carboxylate group. The obtained results clar‐ify another substrate binding mode in D‐amino acid transaminases and underpinned the substrateactivation mechanism.
Добавил в систему: Клячко Наталья Львовна

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To the Understanding of Catalysis by D‐Amino Acid Transaminases: A Case Study of the Enzyme from Aminobacterium colombienseстатья

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