Keenan, T., Cowan, A.R., Flack, E.K.P. et al. (5 more authors) (2024) Structural dissection of the CMP-pseudaminic acid synthetase, PseF. Structure, 32 (12). pp. 2399-2409. ISSN 0969-2126
Abstract
Pseudaminic acid is a non-mammalian sugar found in the surface glycoconjugates of many bacteria, including several human pathogens, and is a virulence factor thought to facilitate immune evasion. The final step in the biosynthesis of the nucleotide activated form of the sugar, CMP-Pse5Ac7Ac is performed by a CMP-Pse5Ac7Ac synthetase (PseF). Here we present the biochemical and structural characterization of PseF from Aeromonas caviae (AcPseF), with AcPseF displaying metal-dependent activity over a broad pH and temperature range. Upon binding to CMP-Pse5Ac7Ac, AcPseF undergoes dynamic movements akin to other CMP-ulosonic acid synthetases. The enzyme clearly discriminates Pse5Ac7Ac from other ulosonic acids, through active site interactions with side-chain functional groups and by positioning the molecule in a hydrophobic pocket. Finally, we show that AcPseF binds the CMP-Pse5Ac7Ac side chain in the lowest energy conformation, a trend that we observed in the structures of other enzymes of this class.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | CMP-Pseudaminic acid synthetase; PseF; pseudaminic acid; CMP-Pseudaminic acidulosonic acid; tg conformation; Aeromonas caviae |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Sep 2024 10:50 |
Last Modified: | 25 Feb 2025 14:58 |
Status: | Published |
Publisher: | Cell Press |
Identification Number: | 10.1016/j.str.2024.09.017 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:217668 |