Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation

ATPPRT is a multi-protein allosteric enzyme where the regulatory protein HisZ enhances catalysis by HisGs. Here, the authors report catalytically impaired active site mutants of HisGs that are allosterically rescued by HisZ despite the HisZ:HisGs interface lying ~20 Å away from the active site.

Bibliographic Details
Main Authors: Gemma Fisher, Marina Corbella, Magnus S. Alphey, John Nicholson, Benjamin J. Read, Shina C. L. Kamerlin, Rafael G. da Silva
Format: Article
Language:English
Published: Nature Portfolio 2022-12-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-022-34960-9
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author Gemma Fisher
Marina Corbella
Magnus S. Alphey
John Nicholson
Benjamin J. Read
Shina C. L. Kamerlin
Rafael G. da Silva
author_facet Gemma Fisher
Marina Corbella
Magnus S. Alphey
John Nicholson
Benjamin J. Read
Shina C. L. Kamerlin
Rafael G. da Silva
author_sort Gemma Fisher
collection DOAJ
description ATPPRT is a multi-protein allosteric enzyme where the regulatory protein HisZ enhances catalysis by HisGs. Here, the authors report catalytically impaired active site mutants of HisGs that are allosterically rescued by HisZ despite the HisZ:HisGs interface lying ~20 Å away from the active site.
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spelling doaj.art-c345a6e16afe41afb597176f4ea0ea082022-12-22T04:19:25ZengNature PortfolioNature Communications2041-17232022-12-0113111510.1038/s41467-022-34960-9Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisationGemma Fisher0Marina Corbella1Magnus S. Alphey2John Nicholson3Benjamin J. Read4Shina C. L. Kamerlin5Rafael G. da Silva6School of Biology, Biomedical Sciences Research Complex, University of St AndrewsScience for Life Laboratory, Department of Chemistry – BMC, Uppsala UniversitySchool of Biology, Biomedical Sciences Research Complex, University of St AndrewsSchool of Biology, Biomedical Sciences Research Complex, University of St AndrewsSchool of Biology, Biomedical Sciences Research Complex, University of St AndrewsScience for Life Laboratory, Department of Chemistry – BMC, Uppsala UniversitySchool of Biology, Biomedical Sciences Research Complex, University of St AndrewsATPPRT is a multi-protein allosteric enzyme where the regulatory protein HisZ enhances catalysis by HisGs. Here, the authors report catalytically impaired active site mutants of HisGs that are allosterically rescued by HisZ despite the HisZ:HisGs interface lying ~20 Å away from the active site.https://doi.org/10.1038/s41467-022-34960-9
spellingShingle Gemma Fisher
Marina Corbella
Magnus S. Alphey
John Nicholson
Benjamin J. Read
Shina C. L. Kamerlin
Rafael G. da Silva
Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation
Nature Communications
title Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation
title_full Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation
title_fullStr Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation
title_full_unstemmed Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation
title_short Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation
title_sort allosteric rescue of catalytically impaired atp phosphoribosyltransferase variants links protein dynamics to active site electrostatic preorganisation
url https://doi.org/10.1038/s41467-022-34960-9
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