Linked Life Data

11087354

Source:http://linkedlifedata.com/resource/pubmed/id/11087354

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2000-12-12
pubmed:databankReference
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14075-81
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11087354-Amino Acid Sequence, pubmed-meshheading:11087354-Chemokine CCL8, pubmed-meshheading:11087354-Chemotaxis, pubmed-meshheading:11087354-Crystallization, pubmed-meshheading:11087354-Crystallography, X-Ray, pubmed-meshheading:11087354-Glutamine, pubmed-meshheading:11087354-Humans, pubmed-meshheading:11087354-Lysine, pubmed-meshheading:11087354-Models, Molecular, pubmed-meshheading:11087354-Molecular Sequence Data, pubmed-meshheading:11087354-Monocyte Chemoattractant Proteins, pubmed-meshheading:11087354-Peptide Fragments, pubmed-meshheading:11087354-Protein Conformation, pubmed-meshheading:11087354-Protein Isoforms, pubmed-meshheading:11087354-Protein Structure, Secondary, pubmed-meshheading:11087354-Pyrrolidonecarboxylic Acid, pubmed-meshheading:11087354-Receptors, Chemokine
pubmed:year
2000
pubmed:articleTitle
Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors.
pubmed:affiliation
Program in Structural Biology and Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, Maryland 21702, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't