title: Chemical modification of a variant of human MIP-1alpha; implications for dimer structure.
abstract: A sequence variant of human MIP-1alpha, in which Asp26 has been replaced by Al alpha, has been chemically modified by the addition of 13C-labeled methyl groups at each of the lysine residues and the N-terminus. The sites of methylation have been verified by a combination of MALDI-TOF mass spectrometric experiments and tryptic digestion followed by N-terminal mapping. The effect of the modification on the structure and activity of the protein have been determined by analytical ultra-centrifugation, 13C NMR spectroscopy and receptor binding studies. The results of these experiments suggest that huMIP-alpha D26A (BB10010), when present as a dimer, adopts a globular structure, like MCP-3, rather than the elongated or cylindrical structure determined for dimers of huMIP-1beta and RANTES.
authors: School of Chemistry, University of Leeds, United Kingdom.
authors: J T
authors: JT
authors: Ashfield
authors: T
authors: T
authors: Meyers
authors: D
authors: D
authors: Lowne
authors: P G
authors: PG
authors: Varley
authors: J R
authors: JR
authors: Arnold
authors: P
authors: P
authors: Tan
authors: J C
authors: JC
authors: Yang
authors: L G
authors: LG
authors: Czaplewski
authors: T
authors: T
authors: Dudgeon
authors: J
authors: J
authors: Fisher
mesh_terms: D000409:Alanine; D019943:Amino Acid Substitution; D001224:Aspartic Acid; D001665:Binding Sites; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000737:chemistry; D019281:Dimerization; D014644:Genetic Variation; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000737:chemistry* / Q000235:genetics*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D019707:Receptors, Chemokine / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014357:Trypsin; D014461:Ultracentrifugation
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D010446:Peptide Fragments; D019707:Receptors, Chemokine; C080633:macrophage inflammatory protein 1alpha receptor; D001224:Aspartic Acid; D014357:Trypsin; D000409:Alanine