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New page: left|200px<br /> <applet load="2fbs" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fbs" /> '''Solution structure of the LL-37 core peptid...
 
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[[Image:2fbs.gif|left|200px]]<br />
<applet load="2fbs" size="450" color="white" frame="true" align="right" spinBox="true"
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'''Solution structure of the LL-37 core peptide bound to detergent micelles'''<br />


==Overview==
==Solution structure of the LL-37 core peptide bound to detergent micelles==
To understand the structure and activity relationship of human LL-37, a, series of peptide fragments was designed. The N-terminal fragment, LL-37(1-12), was not active, while the C-terminal fragment, LL-37(13-37), killed Escherichia coli, as well as drug-sensitive and drug-resistant, cancer cells. A 13-residue core antibacterial and anticancer peptide, corresponding to residues 17-29 of LL-37, was identified based on total, correlated spectroscopy by trimming nonessential regions (TOCSY-trim)., Because LL-37 acts on bacterial membranes, three-dimensional structures of, its fragments were determined in micelles by NMR, including structural, refinement by natural abundance 15N and 13C chemical shifts., Aromatic-aromatic interactions in the N-terminal fragment were proposed to, be essential for LL-37 aggregation. The LL-37 core peptide adopts a, similar structure in the micelles of SDS or dioctanoyl, phosphatidylglycerol. This structure is retained in the C-terminal, fragment LL-37(13-37) and very likely in intact LL-37 based on, peptide-aided signal assignments. The higher antibacterial activity of the, LL-37 core peptide than aurein 1.2 was attributed to additional cationic, residues. To achieve selective membrane targeting, D-amino acids were, incorporated into LL-37(17-32). While the D-peptide showed similar, antibacterial activity to the L-diastereomer, it lost toxicity to human, cells. Structural analysis revealed hydrophobic defects in the new, amphipathic structure of the D-peptide, leading to a much shorter, retention time on a reversed-phase HPLC column. It is proposed that, hydrophobic defects as a result of incoherent hydrophobic packing provide, a structural basis for the improvement in cell selectivity of the LL-37, fragment.
<StructureSection load='2fbs' size='340' side='right'caption='[[2fbs]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2fbs]] 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=2FBS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FBS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=2fbs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fbs OCA], [https://pdbe.org/2fbs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fbs RCSB], [https://www.ebi.ac.uk/pdbsum/2fbs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fbs ProSAT]</span></td></tr>
</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;">
== Publication Abstract from PubMed ==
To understand the structure and activity relationship of human LL-37, a series of peptide fragments was designed. The N-terminal fragment, LL-37(1-12), was not active, while the C-terminal fragment, LL-37(13-37), killed Escherichia coli, as well as drug-sensitive and drug-resistant cancer cells. A 13-residue core antibacterial and anticancer peptide, corresponding to residues 17-29 of LL-37, was identified based on total correlated spectroscopy by trimming nonessential regions (TOCSY-trim). Because LL-37 acts on bacterial membranes, three-dimensional structures of its fragments were determined in micelles by NMR, including structural refinement by natural abundance 15N and 13C chemical shifts. Aromatic-aromatic interactions in the N-terminal fragment were proposed to be essential for LL-37 aggregation. The LL-37 core peptide adopts a similar structure in the micelles of SDS or dioctanoyl phosphatidylglycerol. This structure is retained in the C-terminal fragment LL-37(13-37) and very likely in intact LL-37 based on peptide-aided signal assignments. The higher antibacterial activity of the LL-37 core peptide than aurein 1.2 was attributed to additional cationic residues. To achieve selective membrane targeting, D-amino acids were incorporated into LL-37(17-32). While the D-peptide showed similar antibacterial activity to the L-diastereomer, it lost toxicity to human cells. Structural analysis revealed hydrophobic defects in the new amphipathic structure of the D-peptide, leading to a much shorter retention time on a reversed-phase HPLC column. It is proposed that hydrophobic defects as a result of incoherent hydrophobic packing provide a structural basis for the improvement in cell selectivity of the LL-37 fragment.


==About this Structure==
Solution structures of human LL-37 fragments and NMR-based identification of a minimal membrane-targeting antimicrobial and anticancer region.,Li X, Li Y, Han H, Miller DW, Wang G J Am Chem Soc. 2006 May 3;128(17):5776-85. PMID:16637646<ref>PMID:16637646</ref>
2FBS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FBS OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Solution structures of human LL-37 fragments and NMR-based identification of a minimal membrane-targeting antimicrobial and anticancer region., Li X, Li Y, Han H, Miller DW, Wang G, J Am Chem Soc. 2006 May 3;128(17):5776-85. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16637646 16637646]
</div>
[[Category: Single protein]]
<div class="pdbe-citations 2fbs" style="background-color:#fffaf0;"></div>
[[Category: Li, X.]]
== References ==
[[Category: Li, Y.]]
<references/>
[[Category: Wang, G.]]
__TOC__
[[Category: NH2]]
</StructureSection>
[[Category: amphipathic helix; ll-37; host defense peptide; antimicrobial peptide]]
[[Category: Homo sapiens]]
 
[[Category: Large Structures]]
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:02:37 2007''
[[Category: Li X]]
[[Category: Wang G]]
Retrieved from "https://proteopedia.org/2fbs"