7VZY

The structure of GdmN complex with AMP and 20-O-methyl-19-chloroproansamitocin

Summary for 7VZY

• Entry DOI: 10.2210/pdb7vzy/pdb
• Descriptor: GdmN, (5~{S},6~{E},8~{S},9~{S},12~{R},15~{E})-21-chloranyl-12,20-dimethoxy-6,8,16-trimethyl-5,9-bis(oxidanyl)-2-azabicyclo[16.3.1]docosa-1(21),6,15,18(22),19-pentaene-3,11-dione, FE (III) ION, ... (9 entities in total)
• Functional Keywords: carbamoylation, transferase, ansamycins antibiotics, homodimer
• Biological source: Streptomyces hygroscopicus
• Total number of polymer chains: 2
• Total formula weight: 156248.19

Authors

Wei, J.,Zheng, J.,Zhou, J.,Kang, Q.,Bai, L. (deposition date: 2021-11-17, release date: 2022-11-16, Last modification date: 2023-11-29)

Primary citation

Wei, J.,Zhang, X.,Zhou, Y.,Cheng, X.,Lin, Z.,Tang, M.,Zheng, J.,Wang, B.,Kang, Q.,Bai, L.
Endowing homodimeric carbamoyltransferase GdmN with iterative functions through structural characterization and mechanistic studies.
Nat Commun, 13:6617-6617, 2022

PubMed Abstract: Iterative enzymes, which catalyze sequential reactions, have the potential to improve the atom economy and diversity of industrial enzymatic processes. Redesigning one-step enzymes to be iterative biocatalysts could further enhance these processes. Carbamoyltransferases (CTases) catalyze carbamoylation, an important modification for the bioactivity of many secondary metabolites with pharmaceutical applications. To generate an iterative CTase, we determine the X-ray structure of GdmN, a one-step CTase involved in ansamycin biosynthesis. GdmN forms a face-to-face homodimer through unusual C-terminal domains, a previously unknown functional form for CTases. Structural determination of GdmN complexed with multiple intermediates elucidates the carbamoylation process and identifies key binding residues within a spacious substrate-binding pocket. Further structural and computational analyses enable multi-site enzyme engineering, resulting in an iterative CTase with the capacity for successive 7-O and 3-O carbamoylations. Our findings reveal a subclade of the CTase family and exemplify the potential of protein engineering for generating iterative enzymes.

PubMed: 36329057
DOI: 10.1038/s41467-022-34387-2

Experimental method

X-RAY DIFFRACTION (2.81 Å)