8AHR

Crystal structure of D-amino acid aminotransferase from Aminobacterium colombiense in holo form with PLP

Summary for 8AHR

• Entry DOI: 10.2210/pdb8ahr/pdb
• Descriptor: Aminotransferase class IV, PYRIDOXAL-5'-PHOSPHATE (3 entities in total)
• Functional Keywords: transaminase, daat, aminotransferase, transferase
• Biological source: Aminobacterium colombiense
• Total number of polymer chains: 2
• Total formula weight: 62447.94

Authors

Matyuta, I.O.,Boyko, K.M.,Nikolaeva, A.Y.,Shilova, S.A.,Rakitina, T.V.,Popov, V.O.,Bezsudnova, E.Y. (deposition date: 2022-07-22, release date: 2022-08-03, Last modification date: 2024-02-07)

Primary citation

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, 28:-, 2023

PubMed Abstract: Pyridoxal-5'-phosphate (PLP)-dependent transaminases are highly efficient biocatalysts for stereoselective amination. D-amino acid transaminases can catalyze stereoselective transamination producing optically pure D-amino acids. The knowledge of substrate binding mode and substrate differentiation mechanism in D-amino acid transaminases comes down to the analysis of the transaminase from . However, at least two groups of D-amino acid transaminases differing in the active site organization are known today. Here, we present a detailed study of D-amino acid transaminase from the gram-negative bacterium with a substrate binding mode different from that for the transaminase from . We study the enzyme using kinetic analysis, molecular modeling, and structural analysis of holoenzyme and its complex with D-glutamate. We compare the multipoint binding of D-glutamate with the binding of other substrates, D-aspartate and D-ornithine. QM/MM MD simulation reveals that the substrate can act as a base and its proton can be transferred from the amino group to the α-carboxylate group. This process occurs simultaneously with the nucleophilic attack of the PLP carbon atom by the nitrogen atom of the substrate forming gem-diamine at the transimination step. This explains the absence of the catalytic activity toward ()-amines that lack an α-carboxylate group. The obtained results clarify another substrate binding mode in D-amino acid transaminases and underpinned the substrate activation mechanism.

PubMed: 36903355
DOI: 10.3390/molecules28052109

Experimental method

X-RAY DIFFRACTION (1.9 Å)