Jin, Y., Richards, N.G., Waltho, J.P. orcid.org/0000-0002-7402-5492 et al. (1 more author) (2017) Metal fluorides as analogues for studies on phosphoryl transfer enzymes. Angewandte Chemie International Edition, 56 (15). pp. 4110-4128. ISSN 1433-7851
Abstract
The 1994 structure of a transition state analog with AlF4- and GDP complexed to G1, a small G protein, heralded a new field of research into structure and mechanism of enzymes that manipulate transfer of the phosphoryl (PO3-) group. The list of enzyme structures that embrace metal fluorides, MFx, as ligands that imitate either the phosphoryl group or a phosphate, is now growing at over 80 per triennium. They fall into three distinct geometrical classes: (i) Tetrahedral complexes, based on BeF3-, mimic ground state phosphates; (ii) Octahedral complexes, primarily based on AlF4-, mimic "in-line" anionic transition state for phosphoryl transfer; and (iii) Trigonal bipyramidal complexes, represented by MgF3- and putative AlF30 moieties, additionally mimic the tbp geometry of the transition state. The interpretation of these structures provides a deeper mechanistic understanding of the behavior and manipulation of phosphate monoesters in molecular biology. This review provides a comprehensive overview of these structures, their uses, and their computational development. It questions the identification of AlF30 and MgF4= as tbp species in protein complexes and discusses the relevance of physical organic chemistry and water-based model studies for understanding phosphoryl group transfer in enzymes. It describes two roles for amino acid side-chains that mediate proton transfers during phosphoryl transfer, based on the analysis of protein/MFx structures. First, they deploy hydrogen bonding to neutral oxygen nucleophiles so as to orientate them for correct orbital overlap with the electrophilic phosphorus center. Secondly, they behave as classical general acid/base catalysts.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an author produced version of a paper subsequently published in Angewandte Chemie International Edition. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | 19F NMR spectroscopy; enzyme mechanisms; metal fluorides; phosphoryl transfer; transition-state analogues |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Funding Information: | Funder Grant number HIGHER EDUCATION FUNDING COUNCIL FOR ENGLAND UNSPECIFIED BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL (BBSRC) BB/I002146/1 BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL (BBSRC) BB/E017541/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Jan 2017 15:59 |
Last Modified: | 17 Jul 2023 15:56 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/anie.201606474 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:110427 |