4r8z

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr>

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== Publication Abstract from PubMed ==

The intracellular level of the bacterial secondary messenger, cyclic di-3' ,5' -guanosine monophosphate (c-di-GMP), is determined by a balance between its biosynthesis and degradation, the latter achieved via dedicated phosphodiesterases (PDEs), bearing characteristic EAL or HD-GYP domain. We here report the crystal structure of PA4781, one of the three Pseudomonas aeruginosa HD-GYP proteins, which we have previously characterised in vitro. The structure shows a bi-metallic active site whose metal binding mode is different from both HD-GYP PDEs characterized so far. Purified PA4781 does not contain iron in the active site as for other HD-GYPs, and we show that it binds to a wide range of transition metal with similar affinity. Moreover, the structural features of PA4781 indicate that this is preferentially a pGpG binding protein, as we previously suggested. Our results point out that the structural features of HD-GYPs are more complex than predicted so far, and identify the HD-GYP domain as a conserved scaffold, evolved to preferentially interact with a partner GGDEF, but harbouring different functions obtained through diversification of the active site. IMPORTANCE: In bacteria the capability to form biofilms, responsible for increased pathogenicity and antibiotic resistance, is almost universally stimulated by the second messenger cyclic-di-GMP. To design successful strategies, able target biofilm formation, a detailed characterization of the enzymes involved in c-di-GMP metabolism is crucial. We solved the structure of the HD-GYP domain of PA4781 from Pseudomonas aeruginosa involved in c-di-GMP degradation. This is the third structure of this class of phosphodiesterases to be solved and, with respect to its homologues, shows significant differences both in the nature than in the binding mode of the coordinated metals, indicating that HD-GYP proteins are able to fine-tune their function thereby increasing the chances of the microorganism to adapt to different environmental needs.

The structural basis of functional diversification of HD-GYP domain revealed by the Pseudomonas aeruginosa PA4781 protein displaying an unselective bi-metallic binding site.,Rinaldo S, Paiardini A, Stelitano V, Brunotti P, Cervoni L, Fernicola S, Protano C, Vitali M, Cutruzzola F, Giardina G J Bacteriol. 2015 Feb 17. pii: JB.02606-14. PMID:25691523<ref>PMID:25691523</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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