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PDBsum entry 1esr
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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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Complete crystal structure of monocyte chemotactic protein-2, A cc chemokine that interacts with multiple receptors.
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Authors
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J.Blaszczyk,
E.V.Coillie,
P.Proost,
J.V.Damme,
G.Opdenakker,
G.D.Bujacz,
J.M.Wang,
X.Ji.
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Ref.
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Biochemistry, 2000,
39,
14075-14081.
[DOI no: ]
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PubMed id
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Abstract
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Monocyte chemotactic protein 2 (MCP-2) is a CC chemokine that utilizes multiple
cellular receptors to attract and activate human leukocytes. MCP-2 is a potent
inhibitor of HIV-1 by virtue of its high-affinity binding to the receptor CCR5,
one of the major coreceptors for HIV-1. Although a few structures of CC
chemokines have been reported, none of these was determined with the N-terminal
pyroglutamic acid residue (pGlu1) and a complete C-terminus. pGlu1 is essential
for the chemotactic activity of MCP-2. Recombinant MCP-2 has Gln1 at the N
terminus, 12-15% of which cyclizes automatically and forms pGlu1. The
chemotactic activity of such MCP-2 mixture, which contains 12-15% pGlu1-form and
85-88% Gln1-form protein, is approximately 10 times lower when compared with
that of fully cyclized MCP-2 preparation. Therefore, this chemokine is
practically inactive without pGlu1. We have determined the complete crystal
structure of MCP-2 that contains both pGlu1 and an intact C-terminus. With the
existence of pGlu1, the conformation of the N-terminus allows two additional
interactions between the two subunits of MCP-2 dimer: a hydrogen bond between
pGlu1 and Asn17 and a salt bridge between Asp3 and Arg18. Consequently, both
pGlu1 are anchored and buried, and thereby, both N-terminal regions are
protected against protease degradation. We have also observed not previously
reported extended helical nature of the C terminal region, which covers residues
58-74.
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