Structure of the adenylyl cyclase catalytic core
@article{Zhang1997StructureOT, title={Structure of the adenylyl cyclase catalytic core}, author={Gongyi Zhang and Yu Liu and Arnold E Ruoho and James H. Hurley}, journal={Nature}, year={1997}, volume={386}, pages={247-253} }
Mammalian adenylyl cyclases contain two conserved regions, C1 and C2, which are responsible for forskolin- and G-protein-stimulated catalysis. The structure of the C2 catalytic region of type II rat adenylyl cyclase has an α/β class fold in a wreath-like dimer, which has a central cleft. Two forskolin molecules bind in hydrophobic pockets at the ends of cleft. The central part of the cleft is lined by charged residues implicated in ATP binding. Forskolin appears to activate adenylyl cyclase by…
376 Citations
The adenylyl and guanylyl cyclase superfamily.
- Chemistry, BiologyCurrent opinion in structural biology
- 1998
Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS.
- ChemistryScience
- 1997
The crystal structure of a soluble, catalytically active form of adenylyl cyclase in a complex with its stimulatory heterotrimeric G protein alpha subunit (Gsalpha) and forskolin and structural elements important for substrate recognition and catalysis were identified.
The Structure of a pH-Sensing Mycobacterial Adenylyl Cyclase Holoenzyme
- Chemistry, BiologyScience
- 2005
It is shown that the mycobacterial adenylyl cyclase Rv1264 is rendered a pH sensor by its N-terminal domain, and it is suggested that the transition is regulated by pH.
Conversion of a guanylyl cyclase to an adenylyl cyclase.
- Biology, ChemistryMethods
- 1999
Based on structural data, the replacement of three key residues in the heterodimeric form of soluble guanylyl cyclase has led to a complete conversion in substrate specificity and the mutant enzyme remained fully sensitive to sodium nitroprusside, a nitric oxide donor.
Versatility of signal transduction encoded in dimeric adenylyl cyclases.
- Biology, ChemistryCurrent opinion in structural biology
- 2008
Class III adenylyl cyclases: molecular mechanisms of catalysis and regulation
- Chemistry, BiologyCellular and Molecular Life Sciences
- 2006
Class III adenylyl cyclases are the most abundant type of cyclic AMP-producing enzymes, and regulation usually exploits the dimeric structure of the catalyst, whose active centres form at the dimer interface.
Mutational analysis of the Mycobacterium tuberculosis Rv1625c adenylyl cyclase: residues that confer nucleotide specificity contribute to dimerization
- Biology, ChemistryFEBS letters
- 2003
Crystal Structure of Human Soluble Adenylate Cyclase Reveals a Distinct, Highly Flexible Allosteric Bicarbonate Binding Pocket
- Chemistry, BiologyChemMedChem
- 2014
The first crystal structure of the human enzyme is reported that reveals a pseudosymmetrical arrangement of two catalytic domains to produce a single competent active site and a novel discrete bicarbonate binding pocket.
Substrate selection by class III adenylyl cyclases and guanylyl cyclases
- Biology, ChemistryIUBMB life
- 2005
The second messengers cAMP and cGMP are of central importance in signal transduction pathways and adenylyl and guanylyl cyclases are highly selective for their substrates, ATP and GTP, respectively.
Identification of a Giα Binding Site on Type V Adenylyl Cyclase*
- Biology, ChemistryThe Journal of Biological Chemistry
- 1998
It is demonstrated that myristoylated guanosine 5′-3-O-(thio)triphosphate-Giα1 forms a stable complex with the C1 (but not the C2) domain of type V adenylyl cyclase, suggesting bidirectional regulation of activity by homologous G protein α subunits.
References
SHOWING 1-10 OF 48 REFERENCES
The Conserved Asparagine and Arginine Are Essential for Catalysis of Mammalian Adenylyl Cyclase*
- Biology, ChemistryThe Journal of Biological Chemistry
- 1997
Mammalian adenylyl cyclases have two homologous cytoplasmic domains (C1 and C2), and both domains are required for the high enzymatic activity, and two amino acid residues appear to be crucial for catalysis.
Interaction of the two cytosolic domains of mammalian adenylyl cyclase.
- Biology, ChemistryProceedings of the National Academy of Sciences of the United States of America
- 1996
A model wherein either Gsalpha or forskolin enhances association of the other activator with adenylyl cyclase, as well as facilitating the interaction between the C1 and C2 domains of the enzyme is suggested.
Construction of a soluble adenylyl cyclase activated by Gs alpha and forskolin.
- BiologyScience
- 1995
A soluble adenylyl cyclase was constructed by linkage of portions of the cytosolic domains of the mammalian type I and type II enzymes. The soluble enzyme was stimulated by both forskolin and the…
Characterization and crystallization of a minimal catalytic core domain from mammalian type II adenylyl cyclase
- ChemistryProtein science : a publication of the Protein Society
- 1997
Using limited proteolysis and mass spectrometry, the boundaries of a minimal stable and active C2 catalytic domain are mapped to residues 871–1090 of type II adenylyl cyclase and the properties and crystallization of this trimmed domain are reported, termed IIC2‐Δ4.
Identification of Functional Domains of Adenylyl Cyclase Using in Vivo Chimeras (*)
- BiologyThe Journal of Biological Chemistry
- 1995
Chimeras produced by a novel in vivo mechanism between two differentially modulated adenylyl cyclases to identify their regulatory domains identified a single specific domain of AC1 responsible for calmodulin binding and a small, well defined region near the C terminus of AC2 required for protein kinase C activation.
Two Cytoplasmic Domains of Mammalian Adenylyl Cyclase Form a G- and Forskolin-activated Enzyme in Vitro(*)
- BiologyThe Journal of Biological Chemistry
- 1996
The concentration of IIC-Δ3 needed to complex with IC was reduced 10-fold (0.08 μM) when the enzyme was activated by both forskolin and G, suggesting that G and forSkolin increased the affinity of the two cytoplasmic domains for each other.
Purification and Characterization of a Soluble Form of Mammalian Adenylyl Cyclase*
- BiologyThe Journal of Biological Chemistry
- 1996
An engineered, soluble form of mammalian adenylyl cyclase has been expressed in Escherichia coli and purified by three chromatographic steps, and is activated synergistically by Gsα and forskolin and inhibited directly by the G protein βγ subunit complex.
Complexity and diversity of mammalian adenylyl cyclases.
- BiologyAnnual review of pharmacology and toxicology
- 1996
The discovery of new isoforms of mammalian adenylyl cyclase has revealed unanticipated mechanisms of regulation, including activation or inhibition by the G-protein beta gamma subunit complex, inhibition by G(o) alpha, inhibited by Ca2+, and phosphorylation by protein kinases C and A.
Forskolin: a specific stimulator of adenylyl cyclase or a diterpene with multiple sites of action?
- BiologyTrends in pharmacological sciences
- 1989
Truncation and alanine-scanning mutants of type I adenylyl cyclase.
- BiologyBiochemistry
- 1995
Although the mutations studied have not permitted assignment of unique functions to the two homologous domains, they have revealed novel phenotypes that appear to reflect the regulatory complexity of mammalian membrane-bound adenylyl cyclases, including the possibility of oligomerization of the enzymes.