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| [[Image:1qe6.gif|left|200px]] | | {{Seed}} |
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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)'''
| | ===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. | | The line below this paragraph, {{ABSTRACT_PUBMED_10707023}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 10707023 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_10707023}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Lowman, H.]] | | [[Category: Lowman, H.]] |
| [[Category: Intercrine alpha family]] | | [[Category: Intercrine alpha family]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:10:47 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:11:01 2008'' |
