Structural highlights
Publication Abstract from PubMed
Bacterial hybrid malic enzymes (MaeB grouping, multidomain) catalyse the transformation of malate to pyruvate, and are a major contributor to cellular reducing power and carbon flux. Distinct from other malic enzyme subtypes, the hybrid enzymes are regulated by acetyl-CoA, a molecular indicator of the metabolic state of the cell. Here we solve the structure of a MaeB protein, which reveals hybrid enzymes use the appended phosphotransacetylase (PTA) domain to form a hexameric sensor that communicates acetyl-CoA occupancy to the malic enzyme active site, 60 A away. We demonstrate that allostery is governed by a large-scale rearrangement that rotates the catalytic subunits 70 degrees between the two states, identifying MaeB as a new model enzyme for the study of ligand-induced conformational change. Our work provides the mechanistic basis for metabolic control of hybrid malic enzymes, and identifies inhibition-insensitive variants that may find utility in synthetic biology.
A rotary mechanism for allostery in bacterial hybrid malic enzymes.,Harding CJ, Cadby IT, Moynihan PJ, Lovering AL Nat Commun. 2021 Feb 23;12(1):1228. doi: 10.1038/s41467-021-21528-2. PMID:33623032[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Harding CJ, Cadby IT, Moynihan PJ, Lovering AL. A rotary mechanism for allostery in bacterial hybrid malic enzymes. Nat Commun. 2021 Feb 23;12(1):1228. doi: 10.1038/s41467-021-21528-2. PMID:33623032 doi:http://dx.doi.org/10.1038/s41467-021-21528-2
