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Yorodumi- SASDCK9: Catalytic domain (AC) of B. Pertussis Adenylate Cyclase Toxin (CyaA) -
+Open data
-Basic information
Entry | Database: SASBDB / ID: SASDCK9 |
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Sample | Catalytic domain (AC) of B. Pertussis Adenylate Cyclase Toxin (CyaA)
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Function / homology | Function and homology information calcium- and calmodulin-responsive adenylate cyclase activity / hemolysis in another organism / adenylate cyclase / cAMP biosynthetic process / adenylate cyclase activity / channel activity / toxin activity / positive regulation of cytosolic calcium ion concentration / calmodulin binding / calcium ion binding ...calcium- and calmodulin-responsive adenylate cyclase activity / hemolysis in another organism / adenylate cyclase / cAMP biosynthetic process / adenylate cyclase activity / channel activity / toxin activity / positive regulation of cytosolic calcium ion concentration / calmodulin binding / calcium ion binding / host cell plasma membrane / extracellular region / ATP binding / membrane Similarity search - Function |
Biological species | Bordetella pertussis (strain Tohama I / ATCC BAA-589 / NCTC 13251) (bacteria) |
Citation | Journal: PLoS Biol / Year: 2017 Title: Calmodulin fishing with a structurally disordered bait triggers CyaA catalysis. Authors: Darragh P O'Brien / Dominique Durand / Alexis Voegele / Véronique Hourdel / Marilyne Davi / Julia Chamot-Rooke / Patrice Vachette / Sébastien Brier / Daniel Ladant / Alexandre Chenal / Abstract: Once translocated into the cytosol of target cells, the catalytic domain (AC) of the adenylate cyclase toxin (CyaA), a major virulence factor of Bordetella pertussis, is potently activated by binding ...Once translocated into the cytosol of target cells, the catalytic domain (AC) of the adenylate cyclase toxin (CyaA), a major virulence factor of Bordetella pertussis, is potently activated by binding calmodulin (CaM) to produce supraphysiological levels of cAMP, inducing cell death. Using a combination of small-angle X-ray scattering (SAXS), hydrogen/deuterium exchange mass spectrometry (HDX-MS), and synchrotron radiation circular dichroism (SR-CD), we show that, in the absence of CaM, AC exhibits significant structural disorder, and a 75-residue-long stretch within AC undergoes a disorder-to-order transition upon CaM binding. Beyond this local folding, CaM binding induces long-range allosteric effects that stabilize the distant catalytic site, whilst preserving catalytic loop flexibility. We propose that the high enzymatic activity of AC is due to a tight balance between the CaM-induced decrease of structural flexibility around the catalytic site and the preservation of catalytic loop flexibility, allowing for fast substrate binding and product release. The CaM-induced dampening of AC conformational disorder is likely relevant to other CaM-activated enzymes. |
Contact author |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Data source
SASBDB page | SASDCK9 |
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-Related structure data
Related structure data | C: citing same article (ref.) |
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Similar structure data |
-External links
Related items in Molecule of the Month |
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-Models
Model #1690 | Type: mix / Radius of dummy atoms: 1.90 A / Chi-square value: 2.565 Search similar-shape structures of this assembly by Omokage search (details) |
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Model #1691 | Type: atomic / Radius of dummy atoms: 1.90 A / Chi-square value: 1.358 / P-value: 0.000720 Search similar-shape structures of this assembly by Omokage search (details) |
-Sample
Sample | Name: Catalytic domain (AC) of B. Pertussis Adenylate Cyclase Toxin (CyaA) |
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Buffer | Name: 20 mM Hepes, 150 mM NaCl, 4 mM CaCl2 / pH: 7.4 |
Entity #904 | Name: AC domain from CyaA / Type: protein / Description: Bifunctional hemolysin/adenylate cyclase / Formula weight: 39.38 / Num. of mol.: 1 Source: Bordetella pertussis (strain Tohama I / ATCC BAA-589 / NCTC 13251) References: UniProt: P0DKX7 Sequence: MQQSHQAGYA NAADRESGIP AAVLDGIKAV AKEKNATLMF RLVNPHSTSL IAEGVATKGL GVHAKSSDWG LQAGYIPVNP NLSKLFGRAP EVIARADNDV NSSLAHGHTA VDLTLSKERL DYLRQAGLVT GMADGVVASN HAGYEQFEFR VKETSDGRYA VQYRRKGGDD ...Sequence: MQQSHQAGYA NAADRESGIP AAVLDGIKAV AKEKNATLMF RLVNPHSTSL IAEGVATKGL GVHAKSSDWG LQAGYIPVNP NLSKLFGRAP EVIARADNDV NSSLAHGHTA VDLTLSKERL DYLRQAGLVT GMADGVVASN HAGYEQFEFR VKETSDGRYA VQYRRKGGDD FEAVKVIGNA AGIPLTADID MFAIMPHLSN FRDSARSSVT SGDSVTDYLA RTRRAASEAT GGLDRERIDL LWKIARAGAR SAVGTEARRQ FRYDGDMNIG VITDFELEVR NALNRRAHAV GAQDVVQHGT EQNNPFPEAD EKIFVVSATG ESQMLTRGQL KEYIGQQRGE GYVFYENRAY GVAGKSLFDD GLGA |
-Experimental information
Beam | Instrument name: SOLEIL SWING / City: Saint-Aubin / 国: France / Type of source: X-ray synchrotron / Wavelength: 0.1 Å / Dist. spec. to detc.: 1.988 mm | ||||||||||||||||||||||||||||||||||||||||||
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Detector | Name: AVIEX / Type: CCD | ||||||||||||||||||||||||||||||||||||||||||
Scan | Title: Catalytic domain (AC) of B. Pertussis Adenylate Cyclase Toxin (CyaA) Measurement date: Jun 19, 2015 / Storage temperature: 10 °C / Cell temperature: 15 °C / Exposure time: 1.5 sec. / Number of frames: 250 / Unit: 1/A /
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Distance distribution function P(R) | Sofotware P(R): GNOM 5.0 / Number of points: 773 /
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Result | Type of curve: sec Comments: The scattered intensities were displayed on an absolute scale (cm-1) using the scattering of water. Frames were examined individually and 20 identical frames were averaged and further ...Comments: The scattered intensities were displayed on an absolute scale (cm-1) using the scattering of water. Frames were examined individually and 20 identical frames were averaged and further processed. The corresponding concentration was 0.80 g/L. Three independent determinations of the molecular mass were obtained from the value of I(0)/c, where c is the protein concentration, and using the programs SAXSMow2 and ScÅtter3 available at the URLs http://saxs.ifsc.usp.br/ and https://bl1231.als.lbl.gov/scatter/, respectively. The average value is MWexperimental=40.2 ± 1.0 kDa. AC in solution: Top panel: Adjustment of the curve calculated from the crystal structure of AC extracted from the pdb dataset 1YRU (red curve) after missing loop addition using AllosModFoxs against experimental data (blue dots). chi2=2.57 Bottom panel: Adjustment obtained using AllosModFoxs by releasing residues 200-270 comprising helices F through H’ (red curve). Residues 200-270 correspond to the large yellow-light green loop seen in the model displayed on the right. chi2=1.36
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