1qe6
From Proteopedia
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INTERLEUKIN-8 WITH AN ADDED DISULFIDE BETWEEN RESIDUES 5 AND 33 (L5C/H33C)
Contents |
Overview
The "ELR" (Glu-Leu-Arg) tripeptide sequence near the N-terminus of, interleukin-8 (IL-8) contributes a large part of the receptor binding free, energy. Prior X-ray and nuclear magnetic resonance (NMR) structures of, IL-8 have shown this region of the molecule to be highly mobile. We, reasoned that a hydrophobic interaction between the leucine and the, neighboring beta-turn might exist in the receptor binding conformation of, the N-terminus. To test this hypothesis, we mutated two residues to, cysteine and connected the N-terminus to the beta-turn. The mutant retains, receptor binding affinity reasonably close to wild type and allows the, characterization of a high-affinity conformation that may be useful in the, design of small IL-8 mimics. The L5C/H33C mutant is refined to R-values of, R = 20.6% and Rfree = 27.7% at 2.35 A resolution. Other receptor binding, determinants reside in the "N-loop" found after "ELR" and preceding the, first beta-strand. All available structures of IL-8 have been found with, one of two distinct N-loop conformations. One of these is relevant for, receptor binding, based on NMR results with receptor peptides. The other, conformation obscures the receptor-peptide binding surface and may have an, undetermined but necessarily different function.
Disease
Known disease associated with this structure: AIDS, slow progression to OMIM:[146929]
About this Structure
1QE6 is a Single protein structure of sequence from Homo sapiens with SO4 as ligand. Full crystallographic information is available from OCA.
Reference
Receptor-binding conformation of the "ELR" motif of IL-8: X-ray structure of the L5C/H33C variant at 2.35 A resolution., Gerber N, Lowman H, Artis DR, Eigenbrot C, Proteins. 2000 Mar 1;38(4):361-7. PMID:10707023
Page seeded by OCA on Mon Nov 12 18:52:32 2007
