PDBsum entry 6j4c

Isomerase

PDB id: 6j4c

Contents

Protein chain

123 a.a.

Ligands

GOL

ACY

Metals

_ZN ×3

Waters ×44

PDB id:

6j4c

Name:

Isomerase

Title:

Crystal structure of marh, an epimerase for biosynthesis of maremycins in streptomyces, under 10 mm znso4

Structure:

Cupin superfamily protein. Chain: a. Engineered: yes

Source:

Streptomyces sp. B9173. Organism_taxid: 1462558. Gene: marh. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.58Å R-factor: 0.170 R-free: 0.209

Authors:

Y.Hou,B.Liu,K.Hu,R.Zhang

Key ref:

B.Liu et al. (2019). Structural basis of the mechanism of β-methyl epimerization by enzyme MarH. Org Biomol Chem, 17, 9605-9614. PubMed id: 31681917 DOI: 10.1039/c9ob01996k

Date:

08-Jan-19 Release date: 15-Jan-20

Protein chain

X2D812  (X2D812_9ACTN) -  Cupin superfamily protein from Streptomyces sp. B9173

Seq: 129 a.a.

Struc: 123 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1039/c9ob01996k

Org Biomol Chem 17:9605-9614 (2019)

PubMed id: 31681917

Structural basis of the mechanism of β-methyl epimerization by enzyme MarH.

B.Liu, Y.Hou, X.Wang, X.Ma, S.Fang, T.Huang, Y.Chen, Z.Bai, S.Lin, R.Zhang, K.Hu.

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.