6T70

Structure of the Bottromycin epimerase BotH in complex with Bottromycin A2 derivative

Summary for 6T70

• Entry DOI: 10.2210/pdb6t70/pdb
• Descriptor: BotH, CHLORIDE ION, GLYCEROL, ... (7 entities in total)
• Functional Keywords: bottromycin, ripp, epimerase, abh, hydrolase
• Biological source: Streptomyces sp. BC16019
• Total number of polymer chains: 1
• Total formula weight: 34342.13

Authors

Koehnke, J.,Sikandar, A. (deposition date: 2019-10-20, release date: 2020-07-15, Last modification date: 2024-01-24)

Primary citation

Sikandar, A.,Franz, L.,Adam, S.,Santos-Aberturas, J.,Horbal, L.,Luzhetskyy, A.,Truman, A.W.,Kalinina, O.V.,Koehnke, J.
The bottromycin epimerase BotH defines a group of atypical alpha / beta-hydrolase-fold enzymes.
Nat.Chem.Biol., 16:1013-1018, 2020

PubMed Abstract: D-amino acids endow peptides with diverse, desirable properties, but the post-translational and site-specific epimerization of L-amino acids into their D-counterparts is rare and chemically challenging. Bottromycins are ribosomally synthesized and post-translationally modified peptides that have overcome this challenge and feature a D-aspartate (D-Asp), which was proposed to arise spontaneously during biosynthesis. We have identified the highly unusual α/β-hydrolase (ABH) fold enzyme BotH as a peptide epimerase responsible for the post-translational epimerization of L-Asp to D-Asp during bottromycin biosynthesis. The biochemical characterization of BotH combined with the structures of BotH and the BotH-substrate complex allowed us to propose a mechanism for this reaction. Bioinformatic analyses of BotH homologs show that similar ABH enzymes are found in diverse biosynthetic gene clusters. This places BotH as the founding member of a group of atypical ABH enzymes that may be able to epimerize non-Asp stereocenters across different families of secondary metabolites.

PubMed: 32601484
DOI: 10.1038/s41589-020-0569-y

Experimental method

X-RAY DIFFRACTION (1.58 Å)