This domain is found linked to a wide range of non-homologous domains in a variety of bacteria. It has been shown to be homologous to the adenylyl cyclase catalytic domain [[cite:PUB00007061]] and has diguanylate cyclase activity [[cite:PUB00016966]]. This observation correlates with the functional information available on two GGDEF-containing proteins, namely diguanylate cyclase and phosphodiesterase A of Acetobacter xylinum, both of which regulate the turnover of cyclic diguanosine monophosphate. In the WspR protein of Pseudomonas aeruginosa, the GGDEF domain acts as a diguanylate cyclase, PDB:3bre, when the whole molecule appears to form a tetramer consisting of two symmetrically-related dimers representing a biological unit. The active site is the GGD/EF motif, buried in the structure, and the cyclic dimeric guanosine monophosphate (c-di-GMP) bind to the inhibitory-motif RxxD on the surface. The enzyme thus catalyses the cyclisation of two guanosine triphosphate (GTP) molecules to one c-di-GMP molecule [[cite:PUB00016971],[cite:PUB00109145],[cite:PUB00050740]].
","llm":false,"checked":false,"updated":false}],"wikipedia":[{"title":"GGDEF_domain","extract":"In molecular biology, a GGDEF domain is a protein domain which appears to be ubiquitous in bacteria and is often linked to a regulatory domain, such as a phosphorylation receiver or oxygen sensing domain. Its function is to act as a diguanylate cyclase and synthesize cyclic di-GMP, which is used as an intracellular signalling molecule in a wide variety of bacteria. Enzymatic activity can be strongly influenced by the adjacent domains. Processes regulated by this domain include exopolysaccharide synthesis, biofilm formation, motility and cell differentiation.
","thumbnail":null}],"literature":{"PUB00007150":{"PMID":11557134,"ISBN":null,"volume":"203","issue":"1","year":2001,"title":"Novel domains of the prokaryotic two-component signal transduction systems.","URL":null,"raw_pages":"11-21","medline_journal":"FEMS Microbiol Lett","ISO_journal":"FEMS Microbiol. Lett.","authors":["Galperin MY","Nikolskaya AN","Koonin EV."],"DOI_URL":"http://dx.doi.org/10.1111/j.1574-6968.2001.tb10814.x"},"PUB00016971":{"PMID":15569936,"ISBN":null,"volume":"101","issue":"49","year":2004,"title":"Structural basis of activity and allosteric control of diguanylate cyclase.","URL":null,"raw_pages":"17084-9","medline_journal":"Proc Natl Acad Sci U S A","ISO_journal":"Proc. Natl. Acad. Sci. U.S.A.","authors":["Chan C","Paul R","Samoray D","Amiot NC","Giese B","Jenal U","Schirmer T."],"DOI_URL":"http://dx.doi.org/10.1073/pnas.0406134101"},"PUB00050740":{"PMID":18366254,"ISBN":null,"volume":"6","issue":"3","year":2008,"title":"Phosphorylation-independent regulation of the diguanylate cyclase WspR.","URL":null,"raw_pages":"e67","medline_journal":"PLoS Biol","ISO_journal":"PLoS Biol.","authors":["De N","Pirruccello M","Krasteva PV","Bae N","Raghavan RV","Sondermann H."],"DOI_URL":"http://dx.doi.org/10.1371/journal.pbio.0060067"},"PUB00019612":{"PMID":15142243,"ISBN":null,"volume":"6","issue":"6","year":2004,"title":"Bacterial signal transduction network in a genomic perspective.","URL":null,"raw_pages":"552-67","medline_journal":"Environ Microbiol","ISO_journal":"Environ. Microbiol.","authors":["Galperin MY."],"DOI_URL":"http://dx.doi.org/10.1111/j.1462-2920.2004.00633.x"},"PUB00007061":{"PMID":11119645,"ISBN":null,"volume":"42","issue":"2","year":2001,"title":"GGDEF domain is homologous to adenylyl cyclase.","URL":null,"raw_pages":"210-6","medline_journal":"Proteins","ISO_journal":"Proteins","authors":["Pei J","Grishin NV."],"DOI_URL":"http://dx.doi.org/10.1002/1097-0134(20010201)42:2<210::AID-PROT80>3.0.CO;2-8"},"PUB00109145":{"PMID":16923812,"ISBN":null,"volume":"281","issue":"42","year":2006,"title":"Allosteric control of cyclic di-GMP signaling.","URL":null,"raw_pages":"32015-24","medline_journal":"J Biol Chem","ISO_journal":"J Biol Chem","authors":["Christen B","Christen M","Paul R","Schmid F","Folcher M","Jenoe P","Meuwly M","Jenal U."],"DOI_URL":null},"PUB00019611":{"PMID":15063857,"ISBN":null,"volume":"7","issue":"2","year":2004,"title":"Cyclic di-guanosine-monophosphate comes of age: a novel secondary messenger involved in modulating cell surface structures in bacteria?","URL":null,"raw_pages":"185-91","medline_journal":"Curr Opin Microbiol","ISO_journal":"Curr. Opin. Microbiol.","authors":["Jenal U."],"DOI_URL":"http://dx.doi.org/10.1016/j.mib.2004.02.007"},"PUB00152167":{"PMID":21757706,"ISBN":null,"volume":"286","issue":"36","year":2011,"title":"The atypical two-component sensor kinase Lpl0330 from Legionella pneumophila controls the bifunctional diguanylate cyclase-phosphodiesterase Lpl0329 to modulate bis-(3'-5')-cyclic dimeric GMP synthesis.","URL":null,"raw_pages":"31136-44","medline_journal":"J Biol Chem","ISO_journal":"J Biol Chem","authors":["Levet-Paulo M","Lazzaroni JC","Gilbert C","Atlan D","Doublet P","Vianney A."],"DOI_URL":"https://doi.org/10.1074/jbc.M111.231340"},"PUB00016966":{"PMID":15075296,"ISBN":null,"volume":"18","issue":"6","year":2004,"title":"Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain.","URL":null,"raw_pages":"715-27","medline_journal":"Genes Dev","ISO_journal":"Genes Dev.","authors":["Paul R","Weiser S","Amiot NC","Chan C","Schirmer T","Giese B","Jenal U."],"DOI_URL":"http://dx.doi.org/10.1101/gad.289504"}},"set_info":{"accession":"CL0276","name":"Nucleot_cyclase"},"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":6727,"interactions":0,"matches":240443,"pathways":0,"proteins":238353,"proteomes":13288,"sets":1,"structural_models":{"alphafold":144091},"structures":70,"taxa":19352},"entry_annotations":{"hmm":0,"logo":0,"alignment:seed":44,"alignment:full":113589},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":{"accession":"4yme","name":"Crystal structure of a sensory box/GGDEF family protein (CC_0091) from Caulobacter crescentus CB15 at 1.40 A resolution (PSI Community Target, Shapiro)"}}}