Co-crystal structure provides insights on transaminase CrmG recognition amino donor L-Arg.

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.

• Authors: Rui Chen, Kai Su, Yulong Zhang, Yiguang Zhu, Jinsong Liu, Jinxin Xu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 675 Pg. 41-45 (10 01 2023) ISSN: 1090-2104 [Electronic] United States
• PMID: 37451216 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Chemical References

• Transaminases
• Arginine

Topics

• Transaminases (metabolism)
• Catalytic Domain
• Arginine