|SMART accession number:||SM01118|
|Description:||These sequences are functionally identified as members of the adenylate cyclase family, which catalyses the conversion of ATP to 3',5'-cyclic AMP and pyrophosphate. Six distinct non-homologous classes of AC have been identified. The structure of three classes of adenylyl cyclases have been solved ((PUBMED:16905149)).|
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- Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing CYTH domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with CYTH domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing CYTH domain in the selected taxonomic class.
- Cellular role (predicted cellular role)
Cellular role: metabolism
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Gallagher DT, Smith NN, Kim SK, Heroux A, Robinson H, Reddy PT
- Structure of the class IV adenylyl cyclase reveals a novel fold.
- J Mol Biol. 2006; 362: 114-22
- Display abstract
The crystal structure of the class IV adenylyl cyclase (AC) from Yersinia pestis (Yp) is reported at 1.9 A resolution. The class IV AC fold is distinct from thepreviously described folds for class II and class III ACs. The dimeric AC-IVfolds into an antiparallel eight-stranded barrel whose connectivity has been seenin only three previous structures: yeast RNA triphosphatase and two proteins ofunknown function from Pyrococcus furiosus and Vibrio parahaemolyticus. Eighthighly conserved ionic residues E10, E12, K14, R63, K76, K111, D126, and E136 liein the barrel core and form the likely binding sites for substrate and divalentcations. A phosphate ion is observed bound to R63, K76, K111, and R113 near thecenter of the conserved cluster. Unlike the AC-II and AC-III active sites thatutilize two-Asp motifs for cation binding, the AC-IV active site is relativelyenriched in glutamate and features an ExE motif as its most conserved element.Homologs of Y. pestis AC-IV, including human thiamine triphosphatase, span thethree kingdoms of life and delineate an ancient family of phosphonucleotideprocessing enzymes.
- Smith N, Kim SK, Reddy PT, Gallagher DT
- Crystallization of the class IV adenylyl cyclase from Yersinia pestis.
- Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006; 62: 200-4
- Display abstract
The class IV adenylyl cyclase from Yersinia pestis has been cloned andcrystallized in both a triclinic and an orthorhombic form. An amino-terminalHis-tagged construct, from which the tag was removed by thrombin, crystallized ina triclinic form diffracting to 1.9 A, with one dimer per asymmetric unit andunit-cell parameters a = 33.5, b = 35.5, c = 71.8 A, alpha = 88.7, beta = 82.5,gamma = 65.5 degrees. Several mutants of this construct crystallized butdiffracted poorly. A non-His-tagged native construct (179 amino acids, MW = 20.5 kDa) was purified by conventional chromatography and crystallized in space group P2(1)2(1)2(1). These crystals have unit-cell parameters a = 56.8, b = 118.6, c = 144.5 A, diffract to 3 A and probably have two dimers per asymmetric unit and VM = 3.0 A3 Da(-1). Both crystal forms appear to require pH below 5, complicatingattempts to incorporate nucleotide ligands into the structure. The nativeconstruct has been produced as a selenomethionine derivative and crystallized forphasing and structure determination.
- Iyer LM, Aravind L
- The catalytic domains of thiamine triphosphatase and CyaB-like adenylyl cyclasedefine a novel superfamily of domains that bind organic phosphates.
- BMC Genomics. 2002; 3: 33-33
- Display abstract
BACKGROUND: The CyaB protein from Aeromonas hydrophila has been shown to possess adenylyl cyclase activity. While orthologs of this enzyme have been found in somebacteria and archaea, it shows no detectable relationship to the classicalnucleotide cyclases. Furthermore, the actual biological functions of theseproteins are not clearly understood because they are also present in organisms inwhich there is no evidence for cyclic nucleotide signaling. RESULTS: We show thatthe CyaB like adenylyl cyclase and the mammalian thiamine triphosphatases define a novel superfamily of catalytic domains called the CYTH domain that is presentin all three superkingdoms of life. Using multiple alignments and secondarystructure predictions, we define the catalytic core of these enzymes to contain anovel alpha+beta scaffold with 6 conserved acidic residues and 4 basic residues. Using contextual information obtained from the analysis of gene neighborhoods anddomain fusions, we predict that members of this superfamily may play a centralrole in the interface between nucleotide and polyphosphate metabolism.Additionally, based on contextual information, we identify a novel domain (calledCHAD) that is predicted to functionally interact with the CYTH domain-containing enzymes in bacteria and archaea. The CHAD is predicted to be an alpha helicaldomain, and contains conserved histidines that may be critical for its function. CONCLUSIONS: The phyletic distribution of the CYTH domain suggests that it is an ancient enzymatic domain that was present in the Last Universal Common Ancestorand was involved in nucleotide or organic phosphate metabolism. Based on theconservation of catalytic residues, we predict that CYTH domains are likely tochelate two divalent cations, and exhibit a reaction mechanism that is dependent on two metal ions, analogous to nucleotide cyclases, polymerases and certainphosphoesterases. Our analysis also suggests that the experimentallycharacterized members of this superfamily, namely adenylyl cyclase and thiaminetriphosphatase, are secondary derivatives of proteins that performed an ancientrole in polyphosphate and nucleotide metabolism.
- Sismeiro O, Trotot P, Biville F, Vivares C, Danchin A
- Aeromonas hydrophila adenylyl cyclase 2: a new class of adenylyl cyclases withthermophilic properties and sequence similarities to proteins fromhyperthermophilic archaebacteria.
- J Bacteriol. 1998; 180: 3339-44
- Display abstract
Complementation of an Escherichia coli cya mutant with a genomic library fromAeromonas hydrophila allowed isolation of clones containing two different cyagenes. Whereas one of these genes (cyaA) coded for an adenylyl cyclase (AC1)belonging to the previously described class I adenylyl cyclases (ACs), the secondone (cyaB) coded for a protein (AC2) that did not match any previouslycharacterized protein when compared to protein sequence databases. In particular,it did not align with any of members of the three known classes of ACs. Thepurified AC2 enzyme exhibited remarkable biochemical characteristics, namely, an optimum activity at a high temperature (65 degrees C) and at an alkalinic pH(9.5). In order to investigate the functions of both cyclases in A. hydrophila,each gene was inactivated in the chromosome and the resulting mutant strains wereexamined for physiological alterations. It was shown that, in contrast to cyaA,the cyaB gene was not expressed under usual laboratory growth conditions.However, introduction of a plasmid harboring the cyaB gene in a cyaA mutant, aswell as in a cyaA cyaB mutant, allowed cyclic AMP production. AC2 is the firstmember of a new class of previously unrecognized ACs, and to date, no functional counterpart has been demonstrated in other organisms. However, scanning databasesrevealed a significant similarity between AC2 and the gene product of threehyperthermophilic archaebacteria: Methanobacterium thermoautotrophicum,Archaeglobus fulgidus, and Methanococcus jannaschii. The possibility of a genetransfer between such phylogenetically divergent bacteria is discussed.
- Structure (3D structures containing this domain)
3D Structures of CYTH domains in PDB
PDB code Main view Title 1yem Conserved hypothetical protein Pfu-838710-001 from Pyrococcus furiosus 2aca X-ray structure of a putative adenylate cyclase Q87NV8 from Vibrio parahaemolyticus at the 2.25 A resolution. Northeast Structural Genomics Target VpR19. 2dc4 Structure of PH1012 protein from Pyrococcus Horikoshii OT3 2een Structure of PH1819 protein from Pyrococcus Horikoshii OT3 2fbl The crystal structure of the hypothetical protein NE1496 2fjt Adenylyl cyclase class iv from Yersinia pestis 2gfg Crystal structure of a putative adenylate cyclase (bh2851) from bacillus halodurans at 2.12 A resolution 2jmu NMR structure of the mouse thiamine triphosphatase 3bhd Crystal structure of human thiamine triphosphatase (THTPA) 3n0y Adenylate cyclase class IV with active site ligand APC 3n0z Adenylate cyclase class IV with active site ligand 3AT 3n10 Product complex of adenylate cyclase class IV 3sy3 GBAA_1210 protein, a putative adenylate cyclase, from Bacillus anthracis 3tj7 GBAA_1210 protein, a putative adenylate cyclase, from Bacillus anthracis in complex with AMP 3tvl Complex between the human thiamine triphosphatase and triphosphate 3typ The crystal structure of the inorganic triphosphatase NE1496 3v85 1.9 Angstrom resolution crystal structure of the protein Q9SIY3 from Arabidopsis thaliana
- Links (links to other resources describing this domain)