1esr
From Proteopedia
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, resolution 2.00Å | |||||||
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Ligands: | |||||||
Related: | 1DOK, 1DOL, 1DOM, 1BO0
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Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
Coordinates: | save as pdb, mmCIF, xml |
CRYSTAL STRUCTURE OF HUMAN MONOCYTE CHEMOTACTIC PROTEIN-2
Overview
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.
About this Structure
1ESR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors., Blaszczyk J, Coillie EV, Proost P, Damme JV, Opdenakker G, Bujacz GD, Wang JM, Ji X, Biochemistry. 2000 Nov 21;39(46):14075-81. PMID:11087354
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