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PDBsum entry 1zot

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
1zot
Jmol
Contents
Protein chains
351 a.a. *
69 a.a. *
Ligands
EMA
Metals
_CA ×2
_MG ×3
Waters ×161
* Residue conservation analysis
PDB id:
1zot
Name: Lyase
Title: Crystal structure analysis of the cyaa/c-cam with pmeapp
Structure: Cyaa with c-terminal calmodulin. Chain: a. Fragment: adenylyl cyclase toxin of bordetella pertussis. Engineered: yes. Calmodulin. Chain: b. Fragment: c terminal calmodulin. Engineered: yes
Source: Bordetella pertussis. Organism_taxid: 520. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.
Biol. unit: Dimer (from PQS)
Resolution:
2.20Å     R-factor:   0.252     R-free:   0.291
Authors: Q.Guo,W.J.Tang
Key ref:
Q.Guo et al. (2005). Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin. EMBO J, 24, 3190-3201. PubMed id: 16138079 DOI: 10.1038/sj.emboj.7600800
Date:
13-May-05     Release date:   09-Aug-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam  
P0DKX7  (CYAA_BORPE) -  Bifunctional hemolysin/adenylate cyclase
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1706 a.a.
351 a.a.
Protein chain
Pfam   ArchSchema ?
P62158  (CALM_HUMAN) -  Calmodulin
Seq:
Struc:
149 a.a.
69 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain A: E.C.4.6.1.1  - Adenylate cyclase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP = 3',5'-cyclic AMP + diphosphate
ATP
= 3',5'-cyclic AMP
+ diphosphate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     pathogenesis   1 term 
  Biochemical function     calcium- and calmodulin-responsive adenylate cyclase activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1038/sj.emboj.7600800 EMBO J 24:3190-3201 (2005)
PubMed id: 16138079  
 
 
Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin.
Q.Guo, Y.Shen, Y.S.Lee, C.S.Gibbs, M.Mrksich, W.J.Tang.
 
  ABSTRACT  
 
CyaA is crucial for colonization by Bordetella pertussis, the etiologic agent of whooping cough. Here we report crystal structures of the adenylyl cyclase domain (ACD) of CyaA with the C-terminal domain of calmodulin. Four discrete regions of CyaA bind calcium-loaded calmodulin with a large buried contact surface. Of those, a tryptophan residue (W242) at an alpha-helix of CyaA makes extensive contacts with the calcium-induced, hydrophobic pocket of calmodulin. Mutagenic analyses show that all four regions of CyaA contribute to calmodulin binding and the calmodulin-induced conformational change of CyaA is crucial for catalytic activation. A crystal structure of CyaA-calmodulin with adefovir diphosphate, the metabolite of an approved antiviral drug, reveals the location of catalytic site of CyaA and how adefovir diphosphate tightly binds CyaA. The ACD of CyaA shares a similar structure and mechanism of activation with anthrax edema factor (EF). However, the interactions of CyaA with calmodulin completely diverge from those of EF. This provides molecular details of how two structurally homologous bacterial toxins evolved divergently to bind calmodulin, an evolutionarily conserved calcium sensor.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 Interactions of CaM with CyaA -ACD. (A) Detailed interactions of C-CaM with four discrete regions of CyaA -ACD. C-CaM is colored red and N-CaM is colored in orange. The C-CaM-contact regions, helix F, helices H/H', and the C-terminal tail of CyaA -ACD are colored green, purple, and cyan, respectively. The atoms carbon, oxygen, nitrogen, and sulfur are colored in gray, red, blue, and green, respectively. (B) The interactions of CaM with EF for the comparison. The corresponding CaM contact regions of EF, helix F, and helix H at switch A are colored green and purple, respectively. The two additional CaM contact regions, switch C and the helical domain, are colored cyan and yellow, respectively. (C) Schematic diagram showing the major contact between C-CaM with the helix H of CyaA -ACD and EF. The CaM residues within 4 distance of the indicated residues of CyaA -ACD are boxed.
Figure 7.
Figure 7 Comparison of the interactions of CaM with its effectors. (A) Representative structures of CaM in complex with its effectors. N-CaM is colored orange and C-CaM red. The segment from CaM effectors is colored purple and the second molecule of the dimer of CaM effectors is cyan. The protein data bank accession numbers, 1CDL, 1IWQ, 1L7Z, 1NWD, 1G4Y, and 1YRT, for CaM in complex with MLCK, MARCKS, CAP-23/NAP-22, GAD, calcium-activated small-conductance potassium channel (SK2), and CyaA, respectively. (B) Comparison of the interaction of C-CaM with the H helix of CyaA -ACD and the amphipathic -helix of MLCK. The helices of CaM are colored red and the atoms, carbon, oxygen, nitrogen, and sulfur, are gray, red, blue, and yellow, respectively. (C) Interaction of CaM with its effectors. Sequence and secondary structure of the C-terminal of CaM are shown on the top. The Ca^2+-binding sites are marked and Ca^2+-binding residues are colored red. Boxes beneath the sequence of C-CaM indicate the contact area of each residue in the various structures, using the same coloring scheme as in Figure 4C. The Protein Data Bank codes for the structures are 1CKK, 1CDM, 1IQ5, and 1K90 for CaM in complex with CaM kinase I (CaMKI), CaM kinase II (CaMKII), CaM kinase kinase (CaMKK), and EF, respectively. Helix designations above the CaM sequence are based on the 1CLL CaM structure.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2005, 24, 3190-3201) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21115073 R.Dagher, S.Peng, S.Gioria, M.Fève, M.Zeniou, M.Zimmermann, C.Pigault, J.Haiech, and M.C.Kilhoffer (2011).
A general strategy to characterize calmodulin-calcium complexes involved in CaM-target recognition: DAPK and EGFR calmodulin binding domains interact with different calmodulin-calcium complexes.
  Biochim Biophys Acta, 1813, 1059-1067.  
20534570 E.Laine, C.Goncalves, J.C.Karst, A.Lesnard, S.Rault, W.J.Tang, T.E.Malliavin, D.Ladant, and A.Blondel (2010).
Use of allostery to identify inhibitors of calmodulin-induced activation of Bacillus anthracis edema factor.
  Proc Natl Acad Sci U S A, 107, 11277-11282.  
  20528947 I.Linhartová, L.Bumba, J.Mašín, M.Basler, R.Osička, J.Kamanová, K.Procházková, I.Adkins, J.Hejnová-Holubová, L.Sadílková, J.Morová, and P.Sebo (2010).
RTX proteins: a highly diverse family secreted by a common mechanism.
  FEMS Microbiol Rev, 34, 1076-1112.  
20210554 N.H.Carbonetti (2010).
Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools.
  Future Microbiol, 5, 455-469.  
19186097 R.Shrivastava, and J.F.Miller (2009).
Virulence factor secretion and translocation by Bordetella species.
  Curr Opin Microbiol, 12, 88-93.  
19560485 W.J.Tang, and Q.Guo (2009).
The adenylyl cyclase activity of anthrax edema factor.
  Mol Aspects Med, 30, 423-430.  
18765729 J.L.Larabee, K.DeGiusti, J.L.Regens, and J.D.Ballard (2008).
Bacillus anthracis edema toxin activates nuclear glycogen synthase kinase 3beta.
  Infect Immun, 76, 4895-4904.  
18518982 N.V.Valeyev, D.G.Bates, P.Heslop-Harrison, I.Postlethwaite, and N.V.Kotov (2008).
Elucidating the mechanisms of cooperative calcium-calmodulin interactions: a structural systems biology approach.
  BMC Syst Biol, 2, 48.  
18583346 Q.Guo, J.E.Jureller, J.T.Warren, E.Solomaha, J.Florián, and W.J.Tang (2008).
Protein-protein docking and analysis reveal that two homologous bacterial adenylyl cyclase toxins interact with calmodulin differently.
  J Biol Chem, 283, 23836-23845.  
18272180 R.S.Ampapathi, A.L.Creath, D.I.Lou, J.W.Craft, S.R.Blanke, and G.B.Legge (2008).
Order-disorder-order transitions mediate the activation of cholera toxin.
  J Mol Biol, 377, 748-760.  
17079729 A.Uttenweiler, H.Schwarz, H.Neumann, and A.Mayer (2007).
The vacuolar transporter chaperone (VTC) complex is required for microautophagy.
  Mol Biol Cell, 18, 166-175.  
17942116 J.T.Warren, Q.Guo, and W.J.Tang (2007).
A 1.3-A structure of zinc-bound N-terminal domain of calmodulin elucidates potential early ion-binding step.
  J Mol Biol, 374, 517-527.
PDB code: 2pq3
16406775 J.Vojtova, J.Kamanova, and P.Sebo (2006).
Bordetella adenylate cyclase toxin: a swift saboteur of host defense.
  Curr Opin Microbiol, 9, 69-75.  
17125150 R.L.Rich, and D.G.Myszka (2006).
Survey of the year 2005 commercial optical biosensor literature.
  J Mol Recognit, 19, 478-534.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.