Structural highlights
Publication Abstract from PubMed
Methylmalonyl-CoA epimerase (MMCE) is proposed to use general acid-base catalysis, but the proposed catalytic glutamic acids are highly asymmetrical in the active site unlike many other racemases. To gain insight into the puzzling relationships between catalytic mechanism, structure, and substrate preference, we solved Streptomyces coelicolor MMCE structures with substrate or 2-nitropropionyl-CoA, an intermediate/transition state analogue. Both ligand bound structures have a planar methylmalonate/2-nitropropionyl moiety indicating a deprotonated C2 with >/=4 A distances to either catalytic acid. Both glutamates interact with the carboxylate/nitro group, either directly or through other residues. This suggests the proposed catalytic acids sequentially catalyze proton shifts between C2 and carboxylate of the substrate with an enolate intermediate. In addition, our structures provide a platform to design mutations for expanding substrate scope to support combinatorial biosynthesis.
Substrate Enolate Intermediate and Mimic Captured in the Active Site of Streptomyces coelicolor Methylmalonyl-CoA Epimerase*.,Stunkard LM, Benjamin AB, Bower JB, Huth TJ, Lohman JR Chembiochem. 2021 Dec 1. doi: 10.1002/cbic.202100487. PMID:34856049[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Stunkard LM, Benjamin AB, Bower JB, Huth TJ, Lohman JR. Substrate Enolate Intermediate and Mimic Captured in the Active Site of Streptomyces coelicolor Methylmalonyl-CoA Epimerase*. Chembiochem. 2021 Dec 1. doi: 10.1002/cbic.202100487. PMID:34856049 doi:http://dx.doi.org/10.1002/cbic.202100487
