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PDBsum entry 1i5c
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Signaling protein, transferase
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PDB id
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1i5c
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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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Nucleotide binding by the histidine kinase chea.
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Authors
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A.M.Bilwes,
C.M.Quezada,
L.R.Croal,
B.R.Crane,
M.I.Simon.
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Ref.
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Nat Struct Biol, 2001,
8,
353-360.
[DOI no: ]
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PubMed id
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Abstract
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To probe the structural basis for protein histidine kinase (PHK) catalytic
activity and the prospects for PHK-specific inhibitor design, we report the
crystal structures for the nucleotide binding domain of Thermotoga maritima CheA
with ADP and three ATP analogs (ADPNP, ADPCP and TNP-ATP) bound with either
Mg(2+) or Mn(2+). The conformation of ADPNP bound to CheA and related ATPases
differs from that reported in the ADPNP complex of PHK EnvZ. Interactions of the
active site with the nucleotide gamma-phosphate and its associated Mg(2+) ion
are linked to conformational changes in an ATP-lid that could mediate
recognition of the substrate domain. The inhibitor TNP-ATP binds CheA with its
phosphates in a nonproductive conformation and its adenine and trinitrophenyl
groups in two adjacent binding pockets. The trinitrophenyl interaction may be
exploited for designing CheA-targeted drugs that would not interfere with host
ATPases.
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Figure 1.
Figure 1. Stereo view of ADPCP -Mg2+ bound to P4. Three ADPCP
phosphates, the Asn 409 carbonyl and two water molecules (W6,
W7) coordinate Mg2+ in octahedral geometry (black bonds).
Peptide nitrogens from Gly 506 and Met 507 in the P-loop
(magenta) hydrogen bond to the nucleotide phosphates. The omit
electron density map (green) is contoured at 2.5  .
Figure produced with Bobscript41 and Raster3d^42.
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Figure 3.
Figure 3. Stereo views of the interactions between P4 and bound
nucleotides. a, ADPCP -Mg2+ in MolA hydrogen bonds (dashed
lines) to water molecules (blue spheres, W), protein side chains
in the nucleotide pocket (gray) and the main chain of the
ATP-lid (magenta). b, ADP bound in MolA. c, ADP bound in MolB
has a different conformation for the  -phosphate
than in MolA. Figure produced with Molscript43 and Raster3d^42.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2001,
8,
353-360)
copyright 2001.
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