4h54 | pdb_00004h54
Crystal structure of the diguanylate cyclase DgcZ
Structural highlights
FunctionDGCZ_ECOLI Catalyzes the synthesis of cyclic-di-GMP (c-di-GMP) via the condensation of 2 GTP molecules (PubMed:18713317, PubMed:19460094, PubMed:20582742). May act as a zinc sensor that controls, via c-di-GMP, post-translational events (PubMed:23769666). Overexpression leads to a strong repression of swimming; swimming returnes to normal when residues 206-207 are both mutated to Ala. Overexpression also leads to a reduction in flagellar abundance and a 20-fold increase in c-di-GMP levels in vivo. Required for aminoglycoside-mediated induction of biofilm formation, it also plays a lesser role in biofilm production in response to other classes of translation inhibitors. The c-di-GMP produced by this enzyme up-regulates poly-GlcNAc production as well as the biofilm synthesis protein PgaD, although c-di-GMP is probably not the main inducing principle. C-di-GMP is a second messenger which controls cell surface-associated traits in bacteria (PubMed:19460094).[1] [2] [3] [4] Publication Abstract from PubMedDiguanylate cyclases synthesize the second messenger c-di-GMP, which in turn governs a plethora of physiological processes in bacteria. Although most diguanylate cyclases harbor sensory domains, their input signals are largely unknown. Here, we demonstrate that diguanylate cyclase DgcZ (YdeH) from Escherichia coli is regulated allosterically by zinc. Crystal structures show that the zinc ion is bound to the 3His/1Cys motif of the regulatory chemoreceptor zinc-binding domain, which mediates subunit contact within the dimeric enzyme. In vitro, zinc reversibly inhibits DgcZ with a subfemtomolar Ki constant. In vivo, bacterial biofilm formation is modulated by externally applied zinc in a DgcZ- and c-di-GMP-dependent fashion. The study outlines the structural principles of this zinc sensor. Zinc binding seems to regulate the activity of the catalytic GGDEF domains by impeding their mobility and thus preventing productive encounter of the two GTP substrates. Structure and Signaling Mechanism of a Zinc-Sensory Diguanylate Cyclase.,Zahringer F, Lacanna E, Jenal U, Schirmer T, Boehm A Structure. 2013 Jun 11. pii: S0969-2126(13)00156-1. doi:, 10.1016/j.str.2013.04.026. PMID:23769666[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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