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PDBsum entry 1s26
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Toxin,lyase/metal binding protein
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PDB id
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1s26
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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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Structure of anthrax edema factor-Calmodulin-Adenosine 5'-(Alpha,Beta-Methylene)-Triphosphate complex reveals an alternative mode of ATP binding to the catalytic site.
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Authors
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Y.Shen,
Q.Guo,
N.L.Zhukovskaya,
C.L.Drum,
A.Bohm,
W.J.Tang.
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Ref.
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Biochem Biophys Res Commun, 2004,
317,
309-314.
[DOI no: ]
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PubMed id
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Abstract
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Anthrax edema factor (EF) is a key virulence factor secreted by Bacillus
anthracis. Here, we report a structure, at 3.0 A resolution, of the catalytic
domain of EF (EF3) in complex with calmodulin (CaM) and adenosine
5'-(alpha,beta-methylene)-triphosphate (AMPCPP). Although the binding of the
triphosphate of AMPCPP to EF3 can be superimposed on that of previously
determined 3'deoxy-ATP (3'dATP) and 2'deoxy 3' anthraniloyl-ATP (2'd3' ANT-ATP)
in EF3-CaM, the ribose and the adenine rings of AMPCPP are rotated approximately
105 and 180 degrees, respectively, relative to those of 3'dATP and 2'd3'ANT-ATP.
Based on this model, K382 and F586 should play key roles in the recognition of
adenine. However, mutations of these residues to alanine either separately or
together cause only modest changes in Michaelis-Menten constants and IC50 values
of AMPCPP and cAMP. Therefore, this alternate binding mode of the adenosine of
AMPCPP binds to EF likely playing only a minor role in ATP binding and in
catalysis.
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Secondary reference #1
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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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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
reproduced from the cited reference
with permission from Macmillan Publishers Ltd
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