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PDBsum entry 1zot
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References listed in PDB file
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Key reference
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Title
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Structural basis for the interaction of bordetella pertussis adenylyl cyclase toxin with calmodulin.
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Authors
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Q.Guo,
Y.Shen,
Y.S.Lee,
C.S.Gibbs,
M.Mrksich,
W.J.Tang.
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Ref.
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EMBO J, 2005,
24,
3190-3201.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
70%.
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Abstract
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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.
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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 Å distance of the
indicated residues of CyaA -ACD are boxed.
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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.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
EMBO J
(2005,
24,
3190-3201)
copyright 2005.
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