Download MendeleyCo-crystal structure provides insights on transaminase CrmG recognition amino donor L-Arg.
Chen, R., Su, K., Zhang, Y., Zhu, Y., Liu, J., Xu, J.(2023) Biochem Biophys Res Commun 675: 41-45
- PubMed: 37451216
- DOI: https://doi.org/10.1016/j.bbrc.2023.07.009
- Primary Citation of Related Structures:
8JT3 - 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.
Organizational Affiliation:
Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
