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| - | [[Image:2fbu.gif|left|200px]]<br /> | |
| - | <applet load="2fbu" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="2fbu" /> | |
| - | '''Solution structure of the N-terminal fragment of human LL-37'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Solution structure of the N-terminal fragment of human LL-37== |
| - | 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='2fbu' size='340' side='right'caption='[[2fbu]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[2fbu]] 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=2FBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FBU FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2fbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fbu OCA], [https://pdbe.org/2fbu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fbu RCSB], [https://www.ebi.ac.uk/pdbsum/2fbu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fbu 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> |
| - | 2FBU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FBU OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, 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 2fbu" style="background-color:#fffaf0;"></div> |
| - | [[Category: Li, X.]] | + | == References == |
| - | [[Category: Li, Y.]] | + | <references/> |
| - | [[Category: Wang, G.]] | + | __TOC__ |
| - | [[Category: ll-37; host defense peptide; antimicrobial peptide; aggregation; aromatic-aromatic interaction]]
| + | </StructureSection> |
| - | | + | [[Category: Homo sapiens]] |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:02:43 2007''
| + | [[Category: Large Structures]] |
| | + | [[Category: Li X]] |
| | + | [[Category: Wang G]] |
| Structural highlights
Function
CAMP_HUMAN Binds to bacterial lipopolysaccharides (LPS), has antibacterial activity.[1] [2]
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.
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[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
- ↑ 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
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