PDBsum entry 1yrt

Layse, toxin

PDB id: 1yrt

Contents

Protein chains

351 a.a. *

69 a.a. *

Metals

_CA ×2

Waters ×160

* Residue conservation analysis

PDB id:

1yrt

Name:

Layse, toxin

Title:

Crystal structure analysis of the adenylyl cyclaes catalytic domain of adenylyl cyclase toxin of bordetella pertussis in presence of c- terminal calmodulin

Structure:

Bifunctional hemolysin-adenylate cyclase. Chain: a. Fragment: calmodulin-sensitive adenylate cyclase. Synonym: cyclolysin, act, ac-hly. Engineered: yes. Calmodulin. Chain: b. Synonym: cam, calm, cam1. Engineered: yes

Source:

Bordetella pertussis. Organism_taxid: 520. Gene: cya, cyaa. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Homo sapiens. Human. Organism_taxid: 9606. Gene: calm1, calm2, calm3.

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.220 R-free: 0.270

Authors:

Q.Guo,Y.Shen,Y.S.Lee,C.S.Gibbs,M.Mrksich,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:

04-Feb-05 Release date: 17-Jan-06

Protein chain

P0DKX7  (CYAA_BORPE) -  Bifunctional hemolysin/adenylate cyclase from Bordetella pertussis (strain Tohama I / ATCC BAA-589 / NCTC 13251)

Seq: 1706 a.a.

Struc: 351 a.a.

Protein chain

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 69 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.4.6.1.1 - adenylate cyclase.
• Reaction: ATP = 3',5'-cyclic AMP + diphosphate
• Cofactor: Pyridoxal 5'-phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

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.