PDBsum entry 6j4c

Isomerase

PDB id: 6j4c

Contents

Protein chain

123 a.a.

Ligands

GOL

ACY

Metals

_ZN ×3

Waters ×44

References listed in PDB file

Key reference

• Title: Structural basis of the mechanism of β-Methyl epimerization by enzyme marh.
• Authors: B.Liu, Y.Hou, X.Wang, X.Ma, S.Fang, T.Huang, Y.Chen, Z.Bai, S.Lin, R.Zhang, K.Hu.
• Ref.: Org Biomol Chem, 2019, 17, 9605-9614. [DOI no: 10.1039/c9ob01996k]
• PubMed id: 31681917

Abstract

Diverse derivatives of amino acids with different steric configurations are important biosynthetic building blocks. In biology, epimerization is an important way to generate steric diversity. MarH catalyzes the epimerization of the β-position of (3R)-β-methyl-indolepyruvate (MeInPy), forming (3S)-β-MeInPy. Both compounds are derivatives of l-tryptophan (l-Trp) and are important precursors of bioactive natural products. Here, we report the crystal structures of MarH and the NMR structure of its complex with l-Trp, an analogue of its native substrate, (3R)-β-MeInPy. Structural analysis and mutagenesis studies indicated that His25 acts as a base to remove H_β and generate a planar carbanion intermediate, which is then putatively reprotonated on the opposite face by a water molecule to form (3S)-β-MeInPy in a stereospecific manner. The details of β-site isomerization at the atomic level provide deeper insights into the epimerization mechanism of MarH and will facilitate further enzyme design to extend the substrate scope.