8RDN

Holomycin methyltransferase DtpM with SAH and XRD-271

8RDN の概要

• エントリーDOI: 10.2210/pdb8rdn/pdb
• 関連するPDBエントリー: 8RDM 8RDO
• 分子名称: DtpM, S-ADENOSYL-L-HOMOCYSTEINE, ~{N}-(5-oxidanylidene-4~{H}-[1,2]dithiolo[4,3-b]pyrrol-6-yl)hexanamide, ... (7 entities in total)
• 機能のキーワード: n-methyltransferase, dithiopyrrolone, natural product, xenorabdin, transferase
• 由来する生物種: Xenorhabdus doucetiae FRM16 = DSM 17909
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 156416.21

構造登録者

Huber, E.M.,Groll, M. (登録日: 2023-12-08, 公開日: 2024-10-16, 最終更新日: 2024-12-04)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)