Bellini, Dom and Horrell, Sam and Hutchin, Andrew and Phippen, Curtis W and Strange, Richard W and Cai, Yuming and Wagner, Armin and Webb, Jeremy S and Tews, Ivo and Walsh, Martin A (2017) Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases. Scientific Reports, 7 (1). 42166-. DOI https://doi.org/10.1038/srep42166
Bellini, Dom and Horrell, Sam and Hutchin, Andrew and Phippen, Curtis W and Strange, Richard W and Cai, Yuming and Wagner, Armin and Webb, Jeremy S and Tews, Ivo and Walsh, Martin A (2017) Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases. Scientific Reports, 7 (1). 42166-. DOI https://doi.org/10.1038/srep42166
Bellini, Dom and Horrell, Sam and Hutchin, Andrew and Phippen, Curtis W and Strange, Richard W and Cai, Yuming and Wagner, Armin and Webb, Jeremy S and Tews, Ivo and Walsh, Martin A (2017) Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases. Scientific Reports, 7 (1). 42166-. DOI https://doi.org/10.1038/srep42166
Abstract
<jats:title>Abstract</jats:title><jats:p>The bacterial second messenger cyclic di-3′,5′-guanosine monophosphate (c-di-GMP) is a key regulator of bacterial motility and virulence. As high levels of c-di-GMP are associated with the biofilm lifestyle, c-di-GMP hydrolysing phosphodiesterases (PDEs) have been identified as key targets to aid development of novel strategies to treat chronic infection by exploiting biofilm dispersal. We have studied the EAL signature motif-containing phosphodiesterase domains from the <jats:italic>Pseudomonas aeruginosa</jats:italic> proteins PA3825 (PA3825<jats:sup>EAL</jats:sup>) and PA1727 (MucR<jats:sup>EAL</jats:sup>). Different dimerisation interfaces allow us to identify interface independent principles of enzyme regulation. Unlike previously characterised two-metal binding EAL-phosphodiesterases, PA3825<jats:sup>EAL</jats:sup> in complex with pGpG provides a model for a third metal site. The third metal is positioned to stabilise the negative charge of the 5′-phosphate, and thus three metals could be required for catalysis in analogy to other nucleases. This newly uncovered variation in metal coordination may provide a further level of bacterial PDE regulation.</jats:p>
Item Type: | Article |
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Uncontrolled Keywords: | Pseudomonas aeruginosa; Escherichia coli; Cations, Divalent; Magnesium; Manganese; Phosphoric Diester Hydrolases; Bacterial Proteins; Recombinant Proteins; Cyclic GMP; Crystallography, X-Ray; Cloning, Molecular; Gene Expression; Catalytic Domain; Protein Binding; Substrate Specificity; Hydrolysis; Kinetics; Genetic Vectors; Models, Molecular; Protein Interaction Domains and Motifs; Biocatalysis; Protein Multimerization; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand |
Subjects: | Q Science > QH Natural history > QH301 Biology |
Divisions: | Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 02 Mar 2017 10:17 |
Last Modified: | 07 Aug 2024 19:55 |
URI: | http://repository.essex.ac.uk/id/eprint/19186 |
Available files
Filename: srep42166.pdf
Licence: Creative Commons: Attribution 3.0