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PDBsum entry 1b09
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Immune system
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PDB id
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1b09
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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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The physiological structure of human c-Reactive protein and its complex with phosphocholine.
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Authors
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D.Thompson,
M.B.Pepys,
S.P.Wood.
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Ref.
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Structure Fold Des, 1999,
7,
169-177.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Human C-reactive protein (CRP) is the classical acute phase
reactant, the circulating concentration of which rises rapidly and extensively
in a cytokine-mediated response to tissue injury, infection and inflammation.
Serum CRP values are routinely measured, empirically, to detect and monitor many
human diseases. However, CRP is likely to have important host defence,
scavenging and metabolic functions through its capacity for calcium-dependent
binding to exogenous and autologous molecules containing phosphocholine (PC) and
then activating the classical complement pathway. CRP may also have pathogenic
effects and the recent discovery of a prognostic association between increased
CRP production and coronary atherothrombotic events is of particular interest.
RESUTLS: The X-ray structures of fully calcified C-reactive protein, in the
presence and absence of bound PC, reveal that although the subunit beta-sheet
jellyroll fold is very similar to that of the homologous pentameric protein
serum amyloid P component, each subunit is tipped towards the fivefold axis. PC
is bound in a shallow surface pocket on each subunit, interacting with the two
protein-bound calcium ions via the phosphate group and with Glu81 via the
choline moiety. There is also an unexpected hydrophobic pocket adjacent to the
ligand. CONCLUSIONS: The structure shows how large ligands containing PC may be
bound by CRP via a phosphate oxygen that projects away from the surface of the
protein. Multipoint attachment of one planar face of the CRP molecule to a
PC-bearing surface would leave available, on the opposite exposed face, the
recognition sites for C1q, which have been identified by mutagenesis. This would
enable CRP to target physiologically and/or pathologically significant
complement activation. The hydrophobic pocket adjacent to bound PC invites the
design of inhibitors of CRP binding that may have therapeutic relevance to the
possible role of CRP in atherothrombotic events.
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Figure 3.
Figure 3. Ribbon overlay of an SAP protomer (yellow) and a
CRP protomer (green) indicating the orientation of the protomers
with respect to the fivefold axis of the pentamers.
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The above figure is
reprinted
by permission from Cell Press:
Structure Fold Des
(1999,
7,
169-177)
copyright 1999.
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