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A rotary mechanism for allostery in bacterial hybrid malic enzymes
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dc.contributor.author | Harding, Christopher John | |
dc.contributor.author | Cadby, Ian Thomas | |
dc.contributor.author | Moynihan, Patrick Joseph | |
dc.contributor.author | Lovering, Andrew Lee | |
dc.date.accessioned | 2021-03-12T15:30:16Z | |
dc.date.available | 2021-03-12T15:30:16Z | |
dc.date.issued | 2021-02-23 | |
dc.identifier | 273278216 | |
dc.identifier | b4655fb7-d02b-4bf1-8d26-b0795b75607f | |
dc.identifier | 33623032 | |
dc.identifier | 85101591839 | |
dc.identifier.citation | Harding , C J , Cadby , I T , Moynihan , P J & Lovering , A L 2021 , ' A rotary mechanism for allostery in bacterial hybrid malic enzymes ' , Nature Communications , vol. 12 , 1228 . https://doi.org/10.1038/s41467-021-21528-2 | en |
dc.identifier.issn | 2041-1723 | |
dc.identifier.other | Jisc: a5d58280ca8a406baa07280994e27e10 | |
dc.identifier.other | pii: 10.1038/s41467-021-21528-2 | |
dc.identifier.uri | https://hdl.handle.net/10023/21624 | |
dc.description | This project was funded by BBSRC studentship 1500753 to C.J.H. and a BBSRC David Phillips fellowship to P.J.M. (BB/S010122/1). | en |
dc.description.abstract | 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 Å away. We demonstrate that allostery is governed by a large-scale rearrangement that rotates the catalytic subunits 70° 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. | |
dc.format.extent | 12 | |
dc.format.extent | 4710027 | |
dc.language.iso | eng | |
dc.relation.ispartof | Nature Communications | en |
dc.subject | QD Chemistry | en |
dc.subject | QH301 Biology | en |
dc.subject | DAS | en |
dc.subject.lcc | QD | en |
dc.subject.lcc | QH301 | en |
dc.title | A rotary mechanism for allostery in bacterial hybrid malic enzymes | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.identifier.doi | https://doi.org/10.1038/s41467-021-21528-2 | |
dc.description.status | Peer reviewed | en |
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