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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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* Residue conservation analysis
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PDB id:
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Immune system
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Title:
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Crystal structure of human mcp-1 bound to a blocking antibody, 11k2
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Structure:
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Small inducible cytokine a2. Chain: a. Fragment: monocyte chemotactic protein -1. Synonym: ccl2, monocyte chemotactic protein 1, mcp-1, monocyte chemoattractant protein 1, monocyte chemotactic and activating factor, mcaf, monocyte secretory protein je, hc11. Engineered: yes. Antibody light chain 11k2. Chain: l.
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Source:
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Synthetic: yes. Other_details: chemically synthesized. This sequence occurs naturally in humans. Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: mus musculus. Expression_system_taxid: 10090. Expression_system_cell: murine hybridoma cells.
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Biol. unit:
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Hexamer (from PDB file)
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Resolution:
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2.53Å
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R-factor:
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0.220
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R-free:
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0.277
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Authors:
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P.A.Boriack-Sjodin,M.Rushe,C.Reid,M.Jarpe,H.Van Vlijmen,V.Bailly
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Key ref:
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C.Reid
et al.
(2006).
Structure activity relationships of monocyte chemoattractant proteins in complex with a blocking antibody.
Protein Eng Des Sel,
19,
317-324.
PubMed id:
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Date:
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20-Oct-05
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Release date:
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13-Jun-06
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PROCHECK
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Headers
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References
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P13500
(CCL2_HUMAN) -
C-C motif chemokine 2 from Homo sapiens
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Seq:
Struc:
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99 a.a.
68 a.a.
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Protein Eng Des Sel
19:317-324
(2006)
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PubMed id:
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Structure activity relationships of monocyte chemoattractant proteins in complex with a blocking antibody.
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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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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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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.Sircar,
and
J.J.Gray
(2010).
SnugDock: paratope structural optimization during antibody-antigen docking compensates for errors in antibody homology models.
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PLoS Comput Biol,
6,
e1000644.
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K.W.Kaufmann,
G.H.Lemmon,
S.L.Deluca,
J.H.Sheehan,
and
J.Meiler
(2010).
Practically useful: what the Rosetta protein modeling suite can do for you.
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Biochemistry,
49,
2987-2998.
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T.L.Grygiel,
A.Teplyakov,
G.Obmolova,
N.Stowell,
R.Holland,
J.F.Nemeth,
S.C.Pomerantz,
M.Kruszynski,
and
G.L.Gilliland
(2010).
Synthesis by native chemical ligation and crystal structure of human CCL2.
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Biopolymers,
94,
350-359.
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PDB code:
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S.Fagète,
U.Ravn,
F.Gueneau,
G.Magistrelli,
M.H.Kosco-Vilbois,
and
N.Fischer
(2009).
Specificity tuning of antibody fragments to neutralize two human chemokines with a single agent.
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MAbs,
1,
288-296.
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S.L.Deshmane,
S.Kremlev,
S.Amini,
and
B.E.Sawaya
(2009).
Monocyte chemoattractant protein-1 (MCP-1): an overview.
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J Interferon Cytokine Res,
29,
313-326.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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