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PDBsum entry 1k93
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Toxin,lyase/metal binding protein
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PDB id
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1k93
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Contents |
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* Residue conservation analysis
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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 activation of anthrax adenylyl cyclase exotoxin by calmodulin.
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Authors
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C.L.Drum,
S.Z.Yan,
J.Bard,
Y.Q.Shen,
D.Lu,
S.Soelaiman,
Z.Grabarek,
A.Bohm,
W.J.Tang.
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Ref.
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Nature, 2002,
415,
396-402.
[DOI no: ]
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PubMed id
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Abstract
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Oedema factor, a calmodulin-activated adenylyl cyclase, is important in the
pathogenesis of anthrax. Here we report the X-ray structures of oedema factor
with and without bound calmodulin. Oedema factor shares no significant
structural homology with mammalian adenylyl cyclases or other proteins. In the
active site, 3'-deoxy-ATP and a single metal ion are well positioned for
catalysis with histidine 351 as the catalytic base. This mechanism differs from
the mechanism of two-metal-ion catalysis proposed for mammalian adenylyl
cyclases. Four discrete regions of oedema factor form a surface that recognizes
an extended conformation of calmodulin, which is very different from the
collapsed conformation observed in other structures of calmodulin bound to
effector peptides. On calmodulin binding, an oedema factor helical domain of
relative molecular mass 15,000 undergoes a 15 A translation and a 30 degrees
rotation away from the oedema factor catalytic core, which stabilizes a
disordered loop and leads to enzyme activation. These allosteric changes provide
the first molecular details of how calmodulin modulates one of its targets.
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Figure 3.
Figure 3: CPK representation of EF structures. a, EF alone;
b, CaM -EF. CaM-contacting residues are in red, and the atoms
for switch A, B and C are in cyan, orange and yellow,
respectively.
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Figure 5.
Figure 5: The active site of EF and its comparison with mAC.
a, Ball-and-stick representation of the EF active site. b,
Proposed mechanism of catalysis of EF. For clarity, only
residues that are directly involved in 3' O- to P  nucleophilic
attack are shown. c, Ball-and-stick representation of the mAC
active site. d, Secondary structures of the EF catalytic core
and the mAC catalytic core with the same view as in a and c. The
nucleotide (3'dATP in EF -CaM and ATP- S
in mAC) and the metal ion are in black and grey, respectively.
The O4', C4' and P of
ATP- S
are shown in a similar position to those of 3'dATP in a for
comparison. C1a and C2a of mAC are in green and yellow,
respectively.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2002,
415,
396-402)
copyright 2002.
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