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Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases

Bellini, D and Horrell, S and Hutchin, A and Phippen, CW and Strange, RW and Cai, Y and Wagner, A and Webb, JS and Tews, I and Walsh, MA (2017) 'Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases.' Scientific Reports, 7. ISSN 2045-2322

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Abstract

© The Author(s) 2017. 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 Pseudomonas aeruginosa proteins PA3825 (PA3825 EAL ) and PA1727 (MucR EAL ). Different dimerisation interfaces allow us to identify interface independent principles of enzyme regulation. Unlike previously characterised two-metal binding EAL-phosphodiesterases, PA3825 EAL 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.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 02 Mar 2017 10:17
Last Modified: 20 Aug 2019 16:15
URI: http://repository.essex.ac.uk/id/eprint/19186

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