Structural highlights
Publication Abstract from PubMed
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 (PA3825EAL) and PA1727 (MucREAL). Different dimerisation interfaces allow us to identify interface independent principles of enzyme regulation. Unlike previously characterised two-metal binding EAL-phosphodiesterases, PA3825EAL 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.
Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases.,Bellini D, Horrell S, Hutchin A, Phippen CW, Strange RW, Cai Y, Wagner A, Webb JS, Tews I, Walsh MA Sci Rep. 2017 Feb 10;7:42166. doi: 10.1038/srep42166. PMID:28186120[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bellini D, Horrell S, Hutchin A, Phippen CW, Strange RW, Cai Y, Wagner A, Webb JS, Tews I, Walsh MA. Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases. Sci Rep. 2017 Feb 10;7:42166. doi: 10.1038/srep42166. PMID:28186120 doi:http://dx.doi.org/10.1038/srep42166
