8JT3

Crystal structure of aminotransferase CrmG from Actinoalloteichus sp. WH1-2216-6 in complex with amino donor L-Arg

Summary for 8JT3

• Entry DOI: 10.2210/pdb8jt3/pdb
• Descriptor: CrmG, (E)-N~2~-({3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]pyridin-4-yl}methylidene)-L-arginine, GLYCEROL, ... (5 entities in total)
• Functional Keywords: transaminase, complex, amino donor, transferase
• Biological source: Actinoalloteichus sp. 2216-6
• Total number of polymer chains: 4
• Total formula weight: 231103.00

Authors

Su, K.,Zhang, Y.,Xu, J.,Liu, J. (deposition date: 2023-06-21, release date: 2023-08-02, Last modification date: 2024-05-08)

Primary citation

Chen, R.,Su, K.,Zhang, Y.,Zhu, Y.,Liu, J.,Xu, J.
Co-crystal structure provides insights on transaminase CrmG recognition amino donor L-Arg.
Biochem.Biophys.Res.Commun., 675:41-45, 2023

PubMed Abstract: ω-transaminase has attracted growing attention for chiral amine synthesis, although it commonly suffers from severe by-product inhibition. ω-transaminase CrmG is critical for the biosynthesis of Caerulomycin A, a natural product that possesses broad bioactivity, including immunosuppressive and anti-cancer. Compared to L-Arg, amino donor L-Glu, L-Gln or L-Ala is more preferred by CrmG. In this study, we determined the crystal structure of CrmG in complex with amino donor L-Arg, unveiling the detailed binding mode. Specifically, L-Arg exhibits an extensive contact with aromatic residues F207 and W223 on the roof of CrmG active site via cation-π network. This interaction may render the deamination by-product of L-Arg to be an inhibitor against PMP-bound CrmG by stabilizing its flexible roof, thus reducing the reactivity of L-Arg as an amino donor for CrmG. These data provide further evidence to support our previous proposal that CrmG can overcome inhibition from those by-products that are not able to stabilize the flexible roof of active site in PMP-bound CrmG. Thus, our result can not only facilitate the biosynthesis of CRM A but also be beneficial for the rational design of ω-transaminase to bypass by-product inhibition.

PubMed: 37451216
DOI: 10.1016/j.bbrc.2023.07.009

Experimental method

X-RAY DIFFRACTION (2.35 Å)