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| - | [[Image:1ikm.jpg|left|200px]]<br /><applet load="1ikm" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1ikm" /> | |
| - | '''NMR STUDY OF MONOMERIC HUMAN INTERLEUKIN-8 (30 STRUCTURES)'''<br /> | |
| | | | |
| - | ==Overview== | + | ==NMR study of monomeric human interleukin-8 (30 structures)== |
| - | The solution structure of a monomeric form of interleukin-8 (IL-8) has, been solved using 1H NMR spectroscopy. The chemically synthesized, nonnatural analog [IL-8 (4-72) L25 NH-->NCH3] has the same activity as, that of native IL-8. Thirty structures were generated using the hybrid, distance geometry and simulated annealing protocol using the program, X-PLOR. The structure is well-defined except for N-terminal residues 4-6, and C-terminal residues 67-72. The rms distribution about the average, structure for residues 7-66 is 0.38 A for the backbone atoms and 0.87 A, for all heavy atoms. The structure consists of a series of turns and loops, followed by a triple-stranded beta sheet and a C-terminal alpha helix. The, structure of the monomer is largely similar to the native dimeric IL-8, structures previously determined by both NMR and X-ray methods. The major, difference is that, in the monomeric analog, the C-terminal residues 67-72, are disordered whereas they are helical in the two dimeric structures. The, best fit superposition of the backbone atoms of residues 7-66 of the, monomer structure on the dimeric IL-8 structures showed rms differences of, 1.5 and 1.2 A respectively. The turn (residues 31-35), which is disulfide, linked to the N-terminal region, adopts a conformation in the monomer, similar to that seen in the dimeric X-ray structure (rms difference 1.4 A), and different from that seen in the dimeric NMR structure (rms difference, 2.7 A).(ABSTRACT TRUNCATED AT 250 WORDS) | + | <StructureSection load='1ikm' size='340' side='right'caption='[[1ikm]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1ikm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IKM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IKM FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 30 models</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ikm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ikm OCA], [https://pdbe.org/1ikm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ikm RCSB], [https://www.ebi.ac.uk/pdbsum/1ikm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ikm ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/IL8_HUMAN IL8_HUMAN] IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively.<ref>PMID:2145175</ref> <ref>PMID:2212672</ref> <ref>PMID:11978786</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ik/1ikm_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ikm ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The solution structure of a monomeric form of interleukin-8 (IL-8) has been solved using 1H NMR spectroscopy. The chemically synthesized nonnatural analog [IL-8 (4-72) L25 NH-->NCH3] has the same activity as that of native IL-8. Thirty structures were generated using the hybrid distance geometry and simulated annealing protocol using the program X-PLOR. The structure is well-defined except for N-terminal residues 4-6 and C-terminal residues 67-72. The rms distribution about the average structure for residues 7-66 is 0.38 A for the backbone atoms and 0.87 A for all heavy atoms. The structure consists of a series of turns and loops followed by a triple-stranded beta sheet and a C-terminal alpha helix. The structure of the monomer is largely similar to the native dimeric IL-8 structures previously determined by both NMR and X-ray methods. The major difference is that, in the monomeric analog, the C-terminal residues 67-72 are disordered whereas they are helical in the two dimeric structures. The best fit superposition of the backbone atoms of residues 7-66 of the monomer structure on the dimeric IL-8 structures showed rms differences of 1.5 and 1.2 A respectively. The turn (residues 31-35), which is disulfide linked to the N-terminal region, adopts a conformation in the monomer similar to that seen in the dimeric X-ray structure (rms difference 1.4 A) and different from that seen in the dimeric NMR structure (rms difference 2.7 A).(ABSTRACT TRUNCATED AT 250 WORDS) |
| | | | |
| - | ==Disease==
| + | 1H NMR solution structure of an active monomeric interleukin-8.,Rajarathnam K, Clark-Lewis I, Sykes BD Biochemistry. 1995 Oct 10;34(40):12983-90. PMID:7548056<ref>PMID:7548056</ref> |
| - | Known disease associated with this structure: AIDS, slow progression to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=146929 146929]]
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1IKM 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=CH3:'>CH3</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IKM OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1ikm" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | 1H NMR solution structure of an active monomeric interleukin-8., Rajarathnam K, Clark-Lewis I, Sykes BD, Biochemistry. 1995 Oct 10;34(40):12983-90. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7548056 7548056]
| + | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Clark-Lewis, I.]] | + | [[Category: Clark-Lewis I]] |
| - | [[Category: Rajarathnam, K.]] | + | [[Category: Rajarathnam K]] |
| - | [[Category: Sykes, B.D.]] | + | [[Category: Sykes BD]] |
| - | [[Category: CH3]]
| + | |
| - | [[Category: cytokine (chemotactic)]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:02:02 2008''
| + | |
| Structural highlights
Function
IL8_HUMAN IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The solution structure of a monomeric form of interleukin-8 (IL-8) has been solved using 1H NMR spectroscopy. The chemically synthesized nonnatural analog [IL-8 (4-72) L25 NH-->NCH3] has the same activity as that of native IL-8. Thirty structures were generated using the hybrid distance geometry and simulated annealing protocol using the program X-PLOR. The structure is well-defined except for N-terminal residues 4-6 and C-terminal residues 67-72. The rms distribution about the average structure for residues 7-66 is 0.38 A for the backbone atoms and 0.87 A for all heavy atoms. The structure consists of a series of turns and loops followed by a triple-stranded beta sheet and a C-terminal alpha helix. The structure of the monomer is largely similar to the native dimeric IL-8 structures previously determined by both NMR and X-ray methods. The major difference is that, in the monomeric analog, the C-terminal residues 67-72 are disordered whereas they are helical in the two dimeric structures. The best fit superposition of the backbone atoms of residues 7-66 of the monomer structure on the dimeric IL-8 structures showed rms differences of 1.5 and 1.2 A respectively. The turn (residues 31-35), which is disulfide linked to the N-terminal region, adopts a conformation in the monomer similar to that seen in the dimeric X-ray structure (rms difference 1.4 A) and different from that seen in the dimeric NMR structure (rms difference 2.7 A).(ABSTRACT TRUNCATED AT 250 WORDS)
1H NMR solution structure of an active monomeric interleukin-8.,Rajarathnam K, Clark-Lewis I, Sykes BD Biochemistry. 1995 Oct 10;34(40):12983-90. PMID:7548056[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Van Damme J, Rampart M, Conings R, Decock B, Van Osselaer N, Willems J, Billiau A. The neutrophil-activating proteins interleukin 8 and beta-thromboglobulin: in vitro and in vivo comparison of NH2-terminally processed forms. Eur J Immunol. 1990 Sep;20(9):2113-8. PMID:2145175 doi:http://dx.doi.org/10.1002/eji.1830200933
- ↑ Hebert CA, Luscinskas FW, Kiely JM, Luis EA, Darbonne WC, Bennett GL, Liu CC, Obin MS, Gimbrone MA Jr, Baker JB. Endothelial and leukocyte forms of IL-8. Conversion by thrombin and interactions with neutrophils. J Immunol. 1990 Nov 1;145(9):3033-40. PMID:2212672
- ↑ Schutyser E, Struyf S, Proost P, Opdenakker G, Laureys G, Verhasselt B, Peperstraete L, Van de Putte I, Saccani A, Allavena P, Mantovani A, Van Damme J. Identification of biologically active chemokine isoforms from ascitic fluid and elevated levels of CCL18/pulmonary and activation-regulated chemokine in ovarian carcinoma. J Biol Chem. 2002 Jul 5;277(27):24584-93. Epub 2002 Apr 26. PMID:11978786 doi:http://dx.doi.org/10.1074/jbc.M112275200
- ↑ Rajarathnam K, Clark-Lewis I, Sykes BD. 1H NMR solution structure of an active monomeric interleukin-8. Biochemistry. 1995 Oct 10;34(40):12983-90. PMID:7548056
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