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PDBsum entry 2bdn
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Immune system
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PDB id
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2bdn
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Contents |
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68 a.a.
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214 a.a.
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217 a.a.
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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 activity relationships of monocyte chemoattractant proteins in complex with a blocking antibody.
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Authors
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C.Reid,
M.Rushe,
M.Jarpe,
H.Van vlijmen,
B.Dolinski,
F.Qian,
T.G.Cachero,
H.Cuervo,
M.Yanachkova,
C.Nwankwo,
X.Wang,
N.Etienne,
E.Garber,
V.Bailly,
A.De fougerolles,
P.A.Boriack-Sjodin.
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Ref.
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Protein Eng Des Sel, 2006,
19,
317-324.
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PubMed id
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Abstract
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Monocyte chemoattractant proteins (MCPs) are cytokines that direct immune cells
bearing appropriate receptors to sites of inflammation or injury and are
therefore attractive therapeutic targets for inhibitory molecules. 11K2 is a
blocking mouse monoclonal antibody active against several human and murine MCPs.
A 2.5 A structure of the Fab fragment of this antibody in complex with human
MCP-1 has been solved. The Fab blocks CCR2 receptor binding to MCP-1 through an
adjacent but distinct binding site. The orientation of the Fab indicates that a
single MCP-1 dimer will bind two 11K2 antibodies. Several key residues on the
antibody and on human MCPs were predicted to be involved in antibody
selectivity. Mutational analysis of these residues confirms their involvement in
the antibody-chemokine interaction. In addition to mutations that decreased or
disrupted binding, one antibody mutation resulted in a 70-fold increase in
affinity for human MCP-2. A key residue missing in human MCP-3, a chemokine not
recognized by the antibody, was identified and engineering the preferred residue
into the chemokine conferred binding to the antibody.
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