Falcioni, F. orcid.org/0000-0003-4041-6695, Molt, R.W., Jin, Y. orcid.org/0000-0002-6927-4371 et al. (4 more authors) (2024) Arginine kinase activates arginine for phosphorylation by pyramidalization and polarization. ACS Catalysis, 14 (9). pp. 6650-6658. ISSN 2155-5435
Abstract
Arginine phosphorylation plays numerous roles throughout biology. Arginine kinase (AK) catalyzes the delivery of an anionic phosphoryl group (PO3-) from ATP to a planar, trigonal nitrogen in a guanidinium cation. Density functional theory (DFT) calculations have yielded a model of the transition state (TS) for the AK-catalyzed reaction. They reveal a network of over 50 hydrogen bonds that delivers unprecedented pyramidalization and out-of-plane polarization of the arginine guanidinium nitrogen (Nη2) and aligns the electron density on Nη2 with the scissile P-O bond, leading to in-line phosphoryl transfer via an associative mechanism. In the reverse reaction, the hydrogen-bonding network enforces the conformational distortion of a bound phosphoarginine substrate to increase the basicity of Nη2. This enables Nη2 protonation, which triggers PO3- migration to generate ATP. This polarization-pyramidalization of nitrogen in the arginine side chain is likely a general phenomenon that is exploited by many classes of enzymes mediating the post-translational modification of arginine.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 (https://creativecommons.org/licenses/by/4.0/). |
Keywords: | Anions; Cluster chemistry; Guanidine; Nitrogen; Peptides and proteins |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Funding Information: | Funder Grant number Biotechnology and Biological Sciences Research Council BB/S003320/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 14 May 2024 07:46 |
Last Modified: | 14 May 2024 07:46 |
Status: | Published |
Publisher: | American Chemical Society (ACS) |
Refereed: | Yes |
Identification Number: | 10.1021/acscatal.4c00380 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:212455 |