1qe6
From Proteopedia
(New page: 200px<br /> <applet load="1qe6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qe6, resolution 2.35Å" /> '''INTERLEUKIN-8 WITH ...) |
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| - | [[Image:1qe6.gif|left|200px]]<br /> | + | [[Image:1qe6.gif|left|200px]]<br /><applet load="1qe6" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1qe6" size=" | + | |
caption="1qe6, resolution 2.35Å" /> | caption="1qe6, resolution 2.35Å" /> | ||
'''INTERLEUKIN-8 WITH AN ADDED DISULFIDE BETWEEN RESIDUES 5 AND 33 (L5C/H33C)'''<br /> | '''INTERLEUKIN-8 WITH AN ADDED DISULFIDE BETWEEN RESIDUES 5 AND 33 (L5C/H33C)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The "ELR" (Glu-Leu-Arg) tripeptide sequence near the N-terminus of | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1QE6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1QE6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QE6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Artis, D | + | [[Category: Artis, D R.]] |
[[Category: Eigenbrot, C.]] | [[Category: Eigenbrot, C.]] | ||
[[Category: Gerber, N.]] | [[Category: Gerber, N.]] | ||
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[[Category: intercrine alpha family]] | [[Category: intercrine alpha family]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:38:43 2008'' |
Revision as of 12:38, 21 February 2008
|
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 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
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