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| | ==Solution structure of human LL-23 bound to membrane-mimetic micelles== | | ==Solution structure of human LL-23 bound to membrane-mimetic micelles== |
| - | <StructureSection load='2lmf' size='340' side='right' caption='[[2lmf]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2lmf' size='340' side='right'caption='[[2lmf]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2lmf]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LMF OCA]. <br> | + | <table><tr><td colspan='2'>[[2lmf]] 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=2LMF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LMF FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2k6o|2k6o]]</td></tr>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></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=2lmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lmf OCA], [https://pdbe.org/2lmf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lmf RCSB], [https://www.ebi.ac.uk/pdbsum/2lmf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lmf ProSAT]</span></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lmf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lmf RCSB], [http://www.ebi.ac.uk/pdbsum/2lmf PDBsum]</span></td></tr> | + | </table> |
| - | <table> | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CAMP_HUMAN CAMP_HUMAN] Binds to bacterial lipopolysaccharides (LPS), has antibacterial activity.<ref>PMID:16637646</ref> <ref>PMID:18818205</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | Structure, Dynamics, and Antimicrobial and Immune Modulatory Activities of Human LL-23 and Its Single-Residue Variants Mutated on the Basis of Homologous Primate Cathelicidins.,Wang G, Elliott M, Cogen AL, Ezell EL, Gallo RL, Hancock RE Biochemistry. 2012 Jan 17;51(2):653-64. Epub 2012 Jan 6. PMID:22185690<ref>PMID:22185690</ref> | | Structure, Dynamics, and Antimicrobial and Immune Modulatory Activities of Human LL-23 and Its Single-Residue Variants Mutated on the Basis of Homologous Primate Cathelicidins.,Wang G, Elliott M, Cogen AL, Ezell EL, Gallo RL, Hancock RE Biochemistry. 2012 Jan 17;51(2):653-64. Epub 2012 Jan 6. PMID:22185690<ref>PMID:22185690</ref> |
| | | | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2lmf" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Wang, G.]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Antimicrobial and innate immune modulating peptide]] | + | [[Category: Large Structures]] |
| - | [[Category: Antimicrobial protein]] | + | [[Category: Wang G]] |
| Structural highlights
Function
CAMP_HUMAN Binds to bacterial lipopolysaccharides (LPS), has antibacterial activity.[1] [2]
Publication Abstract from PubMed
LL-23 is a natural peptide corresponding to the 23 N-terminal amino acid residues of human host defense cathelicidin LL-37. LL-23 demonstrated, compared to LL-37, a conserved ability to induce the chemokine MCP-1 in human peripheral blood mononuclear cells, a lack of ability to suppress induction of the pro-inflammatory cytokine TNF-alpha in response to bacterial lipopolysaccharides (LPS), and reduced antimicrobial activity. Heteronuclear multidimensional nuclear magnetic resonance (NMR) characterization of LL-23 revealed similar secondary structures and backbone dynamics in three membrane-mimetic micelles: SDS, dodecylphosphocholine (DPC), and dioctanoylphosphatidylglycerol. The NMR structure of LL-23 determined in perdeuterated DPC contained a unique serine that segregated the hydrophobic surface of the amphipathic helix into two domains. To improve our understanding, Ser9 of LL-23was changed to either Ala or Val on the basis of homologous primate cathelicidins. These changes made the hydrophobic surface of LL-23 continuous and enhanced antibacterial activity. While identical helical structures did not explain the altered activities, a reduced rate of hydrogen-deuterium exchange from LL-23 to LL-23A9 to LL-23V9 suggested a deeper penetration of LL-23V9 into the interior of the micelles, which correlated with enhanced activities. Moreover, these LL-23 variants had discrete immunomodulatory activities. Both restored the TNF-alpha dampening activity to the level of LL-37. Furthermore, LL-23A9, like LL-23, maintained superior protective MCP-1 production, while LL-23V9 was strongly immunosuppressive, preventing baseline MCP-1 induction and substantially reducing LPS-stimulated MCP-1 production. Thus, these LL-23 variants, designed on the basis of a structural hot spot, are promising immune modulators that are easier to synthesize and less toxic to mammalian cells than the parent peptide LL-37.
Structure, Dynamics, and Antimicrobial and Immune Modulatory Activities of Human LL-23 and Its Single-Residue Variants Mutated on the Basis of Homologous Primate Cathelicidins.,Wang G, Elliott M, Cogen AL, Ezell EL, Gallo RL, Hancock RE Biochemistry. 2012 Jan 17;51(2):653-64. Epub 2012 Jan 6. PMID:22185690[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li X, Li Y, Han H, Miller DW, Wang G. Solution structures of human LL-37 fragments and NMR-based identification of a minimal membrane-targeting antimicrobial and anticancer region. J Am Chem Soc. 2006 May 3;128(17):5776-85. PMID:16637646 doi:10.1021/ja0584875
- ↑ Wang G. Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles. J Biol Chem. 2008 Nov 21;283(47):32637-43. Epub 2008 Sep 25. PMID:18818205 doi:10.1074/jbc.M805533200
- ↑ Wang G, Elliott M, Cogen AL, Ezell EL, Gallo RL, Hancock RE. Structure, Dynamics, and Antimicrobial and Immune Modulatory Activities of Human LL-23 and Its Single-Residue Variants Mutated on the Basis of Homologous Primate Cathelicidins. Biochemistry. 2012 Jan 17;51(2):653-64. Epub 2012 Jan 6. PMID:22185690 doi:10.1021/bi2016266
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