| Structural highlights
Function
DGCZ_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 PubMed
Diguanylate 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 Also
References
- ↑ Boehm A, Steiner S, Zaehringer F, Casanova A, Hamburger F, Ritz D, Keck W, Ackermann M, Schirmer T, Jenal U. Second messenger signalling governs Escherichia coli biofilm induction upon ribosomal stress. Mol Microbiol. 2009 Jun;72(6):1500-16. doi: 10.1111/j.1365-2958.2009.06739.x., Epub 2009 May 15. PMID:19460094 doi:10.1111/j.1365-2958.2009.06739.x
- ↑ Zahringer F, Massa C, Schirmer T. Efficient enzymatic production of the bacterial second messenger c-di-GMP by the diguanylate cyclase YdeH from E. coli. Appl Biochem Biotechnol. 2011 Jan;163(1):71-9. doi: 10.1007/s12010-010-9017-x., Epub 2010 Jun 29. PMID:20582742 doi:http://dx.doi.org/10.1007/s12010-010-9017-x
- ↑ Zahringer F, Lacanna E, Jenal U, Schirmer T, Boehm A. Structure and Signaling Mechanism of a Zinc-Sensory Diguanylate Cyclase. Structure. 2013 Jun 11. pii: S0969-2126(13)00156-1. doi:, 10.1016/j.str.2013.04.026. PMID:23769666 doi:10.1016/j.str.2013.04.026
- ↑ Jonas K, Edwards AN, Simm R, Romeo T, Romling U, Melefors O. The RNA binding protein CsrA controls cyclic di-GMP metabolism by directly regulating the expression of GGDEF proteins. Mol Microbiol. 2008 Oct;70(1):236-57. doi: 10.1111/j.1365-2958.2008.06411.x. Epub, 2008 Aug 18. PMID:18713317 doi:http://dx.doi.org/10.1111/j.1365-2958.2008.06411.x
- ↑ Zahringer F, Lacanna E, Jenal U, Schirmer T, Boehm A. Structure and Signaling Mechanism of a Zinc-Sensory Diguanylate Cyclase. Structure. 2013 Jun 11. pii: S0969-2126(13)00156-1. doi:, 10.1016/j.str.2013.04.026. PMID:23769666 doi:10.1016/j.str.2013.04.026
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