Structural highlights
6hvl is a 2 chain structure with sequence from Lismo. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Gene: | dacA, cdaA, lmo2120 (LISMO) |
| Activity: | Diadenylate cyclase, with EC number 2.7.7.85 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[DACA_LISMO] Catalyzes the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP), a signaling compound secreted into the host's cytosol where it triggers the cytosolic surveillance pathway (CSP), a host pathway of innate immunity characterized by expression of beta interferon (IFN-beta) and coregulated genes.[1]
Publication Abstract from PubMed
Cyclic di-AMP (c-di-AMP) is the only second messenger known to be essential for bacterial growth. It has been mainly found in gram-positive bacteria, including pathogenic bacteria like Listeria monocytogenes. CdaA is the sole di-adenylate cyclase in L. monocytogenes rendering this enzyme an attractive target for the development of novel antibiotic compounds. Here we report crystal structures of CdaA from L. monocytogenes in the apo-state, in the post-catalytic state with bound c-di-AMP and catalytic Co2+ ions, as well as in a complex with AMP. These structures reveal the flexibility of a tyrosine side-chain involved in locking the adenine ring after ATP binding. The essential role of this tyrosine was confirmed by mutation to Ala leading to a drastic loss of enzymatic activity.
Crystal structures of the c-di-AMP synthesizing enzyme CdaA.,Heidemann JL, Neumann P, Dickmanns A, Ficner R J Biol Chem. 2019 May 22. pii: RA119.009246. doi: 10.1074/jbc.RA119.009246. PMID:31118276[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Woodward JJ, Iavarone AT, Portnoy DA. c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science. 2010 Jun 25;328(5986):1703-5. doi: 10.1126/science.1189801. Epub 2010, May 27. PMID:20508090 doi:http://dx.doi.org/10.1126/science.1189801
- ↑ Heidemann JL, Neumann P, Dickmanns A, Ficner R. Crystal structures of the c-di-AMP synthesizing enzyme CdaA. J Biol Chem. 2019 May 22. pii: RA119.009246. doi: 10.1074/jbc.RA119.009246. PMID:31118276 doi:http://dx.doi.org/10.1074/jbc.RA119.009246
