title: Bifunctional structure of two adenylyl cyclases from the myxobacterium Stigmatella aurantiaca.
abstract: Two adenylyl cyclase genes (cyaA and cyaB) from the myxobacterium Stigmatella aurantiaca were cloned by complementation of Escherichia coli mutants defective in the cya gene. cyaA codes for a protein of 424 amino acid residues (AC1), while cyaB encodes a protein of 352 residues (AC2). Both cyclases are sensitive to adenosine: cAMP production was strongly inhibited in E coli cells and cell extracts expressing these genes. AC1 comprises a hydrophobic domain of six transmembrane helices coupled to a cytoplasmic catalytic domain endowed with adenylyl cyclase activity. A 17 amino acid residue sequence, which is a signature of G-protein coupled receptors, as well as of slime mold Dictyostelium discoideum cyclic AMP receptors, was found in the membrane domain. AC2 displays features also indicating that it is a bifunctional enzyme. The domain located upstream from the catalytic adenylyl cyclase domain shows strong similarity to receiver modules of response regulators of two-component bacterial signaling systems. In vitro mutagenesis of conserved aspartate residues in this domain was shown to interfere with cAMP synthesis.
authors.affiliation: DKFZ, Deutsches Krebs Forschung Zentrum, Heidelberg, Germany.
authors.forename: M P
authors.initials: MP
authors.lastname: Coudart-Cavalli
authors.forename: O
authors.initials: O
authors.lastname: Sismeiro
authors.forename: A
authors.initials: A
authors.lastname: Danchin
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D001483:Base Sequence; D000242:Cyclic AMP / Q000096:biosynthesis; D004252:DNA Mutational Analysis; D004789:Enzyme Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D009231:Myxococcales / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D037361:Adenylate Cyclase Toxin; D001426:Bacterial Proteins; D011498:Protein Precursors; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000241:Adenosine