8RDM

Holomycin methyltransferase DtpM with SAH

Summary for 8RDM

• Entry DOI: 10.2210/pdb8rdm/pdb
• Related: 8RDL 8RDN 8RDO
• Descriptor: DtpM, S-ADENOSYL-L-HOMOCYSTEINE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: n-methyltransferase, dithiopyrrolone, natural product, xenorabdin, transferase
• Biological source: Xenorhabdus doucetiae FRM16 = DSM 17909
• Total number of polymer chains: 1
• Total formula weight: 38951.01

Authors

Huber, E.M.,Groll, M. (deposition date: 2023-12-08, release date: 2024-10-16, Last modification date: 2024-12-04)

Primary citation

Su, L.,Huber, E.M.,Westphalen, M.,Gellner, J.,Bode, E.,Kobel, T.,Grun, P.,Alanjary, M.M.,Glatter, T.,Cirnski, K.,Muller, R.,Schindler, D.,Groll, M.,Bode, H.B.
Isofunctional but Structurally Different Methyltransferases for Dithiolopyrrolone Diversification.
Angew.Chem.Int.Ed.Engl., 63:e202410799-e202410799, 2024

PubMed Abstract: Dithiolopyrrolone (DTP) natural products are produced by several different bacteria and have potent antibacterial, antifungal and anticancer activities. While the amide of their DTP core can be methylated to fine-tune bioactivity, the enzyme responsible for the amide N-methylation has remained elusive in most taxa. Here, we identified the amide methyltransferase XrdM that is responsible for xenorhabdin (XRD) methylation in Xenorhabdus doucetiae but encoded outside of the XRD gene cluster. XrdM turned out to be isofunctional with the recently reported methyltransferase DtpM, that is involved in the biosynthesis of the DTP thiolutin, although its X-ray structure is unrelated to that of DtpM. To investigate the structural basis for ligand binding in both enzymes, we used X-ray crystallography, modeling, site-directed mutagenesis, and kinetic activity assays. Our study expands the limited knowledge of post-non-ribosomal peptide synthetase (NRPS) amide methylation in DTP biosynthesis and reveals an example of convergent evolution of two structurally completely different enzymes for the same reaction in different organisms.

PubMed: 39185606
DOI: 10.1002/anie.202410799

Experimental method

X-RAY DIFFRACTION (1.75 Å)