1qe6

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{{STRUCTURE_1qe6| PDB=1qe6 | SCENE= }}
{{STRUCTURE_1qe6| PDB=1qe6 | SCENE= }}
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'''INTERLEUKIN-8 WITH AN ADDED DISULFIDE BETWEEN RESIDUES 5 AND 33 (L5C/H33C)'''
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===INTERLEUKIN-8 WITH AN ADDED DISULFIDE BETWEEN RESIDUES 5 AND 33 (L5C/H33C)===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_10707023}}
==About this Structure==
==About this Structure==
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[[Category: Lowman, H.]]
[[Category: Lowman, H.]]
[[Category: Intercrine alpha family]]
[[Category: Intercrine alpha family]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:11:01 2008''

Revision as of 12:11, 29 July 2008

Template:STRUCTURE 1qe6

INTERLEUKIN-8 WITH AN ADDED DISULFIDE BETWEEN RESIDUES 5 AND 33 (L5C/H33C)

Template:ABSTRACT PUBMED 10707023

About this Structure

1QE6 is a Single protein structure of sequence from Homo sapiens. 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

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