| IED ID | IndEnz0002004450 |
| Enzyme Type ID | protease004450 |
| Protein Name |
Calmodulin-sensitive adenylate cyclase EC 4.6.1.1 ATP pyrophosphate-lyase Adenylyl cyclase Anthrax edema toxin adenylate cyclase component Edema factor EF |
| Gene Name | cya pXO1-122 BXA0141 GBAA_pXO1_0142 |
| Organism | Bacillus anthracis |
| Taxonomic Lineage | cellular organisms Bacteria Terrabacteria group Firmicutes Bacilli Bacillales Bacillaceae Bacillus Bacillus cereus group Bacillus anthracis |
| Enzyme Sequence | MTRNKFIPNKFSIISFSVLLFAISSSQAIEVNAMNEHYTESDIKRNHKTEKNKTEKEKFKDSINNLVKTEFTNETLDKIQQTQDLLKKIPKDVLEIYSELGGEIYFTDIDLVEHKELQDLSEEEKNSMNSRGEKVPFASRFVFEKKRETPKLIINIKDYAINSEQSKEVYYEIGKGISLDIISKDKSLDPEFLNLIKSLSDDSDSSDLLFSQKFKEKLELNNKSIDINFIKENLTEFQHAFSLAFSYYFAPDHRTVLELYAPDMFEYMNKLEKGGFEKISESLKKEGVEKDRIDVLKGEKALKASGLVPEHADAFKKIARELNTYILFRPVNKLATNLIKSGVATKGLNVHGKSSDWGPVAGYIPFDQDLSKKHGQQLAVEKGNLENKKSITEHEGEIGKIPLKLDHLRIEELKENGIILKGKKEIDNGKKYYLLESNNQVYEFRISDENNEVQYKTKEGKITVLGEKFNWRNIEVMAKNVEGVLKPLTADYDLFALAPSLTEIKKQIPQKEWDKVVNTPNSLEKQKGVTNLLIKYGIERKPDSTKGTLSNWQKQMLDRLNEAVKYTGYTGGDVVNHGTEQDNEEFPEKDNEIFIINPEGEFILTKNWEMTGRFIEKNITGKDYLYYFNRSYNKIAPGNKAYIEWTDPITKAKINTIPTSAEFIKNLSSIRRSSNVGVYKDSGDKDEFAKKESVKKIAGYLSDYYNSANHIFSQEKKRKISIFRGIQAYNEIENVLKSKQIAPEYKNYFQYLKERITNQVQLLLTHQKSNIEFKLLYKQLNFTENETDNFEVFQKIIDEK |
| Enzyme Length | 800 |
| Uniprot Accession Number | P40136 |
| Absorption | |
| Active Site | ACT_SITE 351; /note=Proton acceptor; /evidence=ECO:0000269|PubMed:11807546 |
| Activity Regulation | ACTIVITY REGULATION: Host calmodulin is an absolute requirement for its activation (PubMed:2114169, PubMed:11807546). Inhibited by ethyl 5-aminopyrazolo[1,5-a]quinazoline-3-carboxylate (PubMed:12676933). {ECO:0000269|PubMed:11807546, ECO:0000269|PubMed:12676933, ECO:0000269|PubMed:2114169}. |
| Binding Site | BINDING 548; /note="3',5'-cyclic AMP; via amide nitrogen and carbonyl oxygen"; /evidence="ECO:0000269|PubMed:15719022, ECO:0007744|PDB:1XFW" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1; Evidence={ECO:0000269|PubMed:11807546, ECO:0000269|PubMed:2108958, ECO:0000269|PubMed:6285339}; |
| DNA Binding | |
| EC Number | 4.6.1.1 |
| Enzyme Function | FUNCTION: Edema factor (EF), which constitutes one of the three proteins composing the anthrax toxin, causes edema in the host (PubMed:6285339, PubMed:2108958, PubMed:11807546). Acts as a calmodulin-dependent adenylyl cyclase by converting ATP to cAMP, leading to dramatic elevation of intracellular cAMP levels in the host, thereby causing edema (PubMed:6285339, PubMed:2108958, PubMed:11807546). EF is not toxic by itself and only acts as a edema factor when associated with protective antigen (PA) to form the edema toxin (EdTx) (PubMed:11553601, PubMed:2108958). Required for the survival of germinated spores within macrophages at the early stages of infection (PubMed:11737637). {ECO:0000269|PubMed:11553601, ECO:0000269|PubMed:11737637, ECO:0000269|PubMed:11807546, ECO:0000269|PubMed:2108958, ECO:0000269|PubMed:6285339}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 577..579; /note="3',5'-cyclic AMP"; /evidence="ECO:0000269|PubMed:15719022, ECO:0007744|PDB:1XFW" |
| Features | Active site (1); Beta strand (41); Binding site (1); Chain (1); Domain (1); Helix (32); Metal binding (3); Mutagenesis (26); Nucleotide binding (1); Region (4); Sequence conflict (4); Signal peptide (1); Turn (18) |
| Keywords | 3D-structure;ATP-binding;Calcium;Calmodulin-binding;Direct protein sequencing;Host cytoplasm;Lyase;Magnesium;Metal-binding;Nucleotide-binding;Plasmid;Reference proteome;Secreted;Signal;Toxin;Virulence;cAMP biosynthesis |
| Interact With | P62155; P0DP24 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:3149607}. Host cytoplasm, host cytosol {ECO:0000269|PubMed:1512256}. Note=Translocation into host cytosol is mediated via interaction with the cleaved form of protective antigen (PA-63): following secretion, EF binds via its N-terminal region to the upper rim of the ring-shaped homooligomer (homoheptamer or homooctamer) formed by PA-63 on the host cell membrane (PubMed:32047164). In this PA-63 pre-pore state, the N-terminal segment of EF refolds into an alpha helix engaged in the alpha-clamp of the PA-63 pre-pore (PubMed:32047164, PubMed:32521227). Recruitment to the PA-63 pre-pore enables domain reorganization of EF (PubMed:32521227). Loaded complexes are then endocytosed, followed by a conformational change of oligomerized PA-63 from the pre-pore to pore state, which is triggered by the low pH in the endosome (PubMed:11207582). EF is then unfolded to pass through the PA-63 pore and translocate into the host cytosol (PubMed:32047164). {ECO:0000269|PubMed:11207582, ECO:0000269|PubMed:32047164, ECO:0000269|PubMed:32521227}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | SIGNAL 1..33; /evidence=ECO:0000269|PubMed:3149607 |
| Structure 3D | Electron microscopy (4); X-ray crystallography (14) |
| Cross Reference PDB | 1K8T; 1K90; 1K93; 1LVC; 1PK0; 1S26; 1SK6; 1XFU; 1XFV; 1XFW; 1XFX; 1XFY; 1XFZ; 1Y0V; 6UZB; 6UZD; 6UZE; 6VRA; |
| Mapped Pubmed ID | 11790132; 12485993; 12724328; 14978283; 15063758; 15131111; |
| Motif | |
| Gene Encoded By | Plasmid pXO1 |
| Mass | 92,478 |
| Kinetics | |
| Metal Binding | METAL 491; /note="Magnesium"; /evidence="ECO:0000269|PubMed:15719022, ECO:0007744|PDB:1XFU, ECO:0007744|PDB:1XFV, ECO:0007744|PDB:1XFW, ECO:0007744|PDB:1XFX, ECO:0007744|PDB:1XFY, ECO:0007744|PDB:1XFZ, ECO:0007744|PDB:1Y0V"; METAL 493; /note="Magnesium"; /evidence="ECO:0000269|PubMed:15719022, ECO:0007744|PDB:1XFU, ECO:0007744|PDB:1XFV, ECO:0007744|PDB:1XFW, ECO:0007744|PDB:1XFX, ECO:0007744|PDB:1XFY, ECO:0007744|PDB:1XFZ, ECO:0007744|PDB:1Y0V"; METAL 577; /note="Magnesium; via tele nitrogen"; /evidence="ECO:0000269|PubMed:15719022, ECO:0007744|PDB:1XFU, ECO:0007744|PDB:1XFV, ECO:0007744|PDB:1XFW, ECO:0007744|PDB:1XFX, ECO:0007744|PDB:1XFY, ECO:0007744|PDB:1XFZ, ECO:0007744|PDB:1Y0V" |
| Rhea ID | RHEA:15389 |
| Cross Reference Brenda |