PDBsum entry 6t6x

Hydrolase

PDB id: 6t6x

Contents

Protein chain

253 a.a.

Ligands

MQW

Waters ×306

PDB id:

6t6x

Name:

Hydrolase

Title:

Structure of the bottromycin epimerase both in complex with substrate

Structure:

Both. Chain: a. Engineered: yes

Source:

Streptomyces sp. Bc16019. Organism_taxid: 1109705. Gene: both. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: rosetta 2

Resolution:

1.25Å R-factor: 0.167 R-free: 0.175

Authors:

J.Koehnke,A.Sikandar

Key ref:

A.Sikandar et al. (2020). The bottromycin epimerase BotH defines a group of atypical α/β-hydrolase-fold enzymes. Nat Chem Biol, 16, 1013-1018. PubMed id: 32601484

Date:

20-Oct-19 Release date: 15-Jul-20

Protein chain

K4MHV9  (K4MHV9_9ACTN) -  BotH from Streptomyces sp. BC16019

Seq: 293 a.a.

Struc: 253 a.a.

Nat Chem Biol 16:1013-1018 (2020)

PubMed id: 32601484

The bottromycin epimerase BotH defines a group of atypical α/β-hydrolase-fold enzymes.

A.Sikandar, L.Franz, S.Adam, J.Santos-Aberturas, L.Horbal, A.Luzhetskyy, A.W.Truman, O.V.Kalinina, J.Koehnke.

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.