6J4C

Crystal structure of MarH, an epimerase for biosynthesis of Maremycins in Streptomyces, under 10 mM ZnSO4

Summary for 6J4C

• Entry DOI: 10.2210/pdb6j4c/pdb
• Related: 6J4B 6J4D
• Descriptor: Cupin superfamily protein, ZINC ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: isomerase, epimerase, maremycins, biosynthesis
• Biological source: Streptomyces sp. B9173
• Total number of polymer chains: 1
• Total formula weight: 13671.66

Authors

Hou, Y.,Liu, B.,Hu, K.,Zhang, R. (deposition date: 2019-01-08, release date: 2020-01-15, Last modification date: 2024-03-27)

Primary citation

Liu, B.,Hou, Y.,Wang, X.,Ma, X.,Fang, S.,Huang, T.,Chen, Y.,Bai, Z.,Lin, S.,Zhang, R.,Hu, K.
Structural basis of the mechanism of beta-methyl epimerization by enzyme MarH.
Org.Biomol.Chem., 17:9605-9614, 2019

PubMed 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 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.

PubMed: 31681917
DOI: 10.1039/c9ob01996k

Experimental method

X-RAY DIFFRACTION (1.58 Å)