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| | ==Crystal structure of the cathelin-like domain of human cathelicidin LL-37 (hCLD)== | | ==Crystal structure of the cathelin-like domain of human cathelicidin LL-37 (hCLD)== |
| - | <StructureSection load='4eyc' size='340' side='right' caption='[[4eyc]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4eyc' size='340' side='right'caption='[[4eyc]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4eyc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EYC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EYC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4eyc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EYC FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pfp|1pfp]], [[1lxe|1lxe]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CAMP, CAP18, FALL39, HSD26 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4eyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eyc OCA], [https://pdbe.org/4eyc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eyc RCSB], [https://www.ebi.ac.uk/pdbsum/4eyc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eyc ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eyc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eyc RCSB], [http://www.ebi.ac.uk/pdbsum/4eyc PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CAMP_HUMAN CAMP_HUMAN]] Binds to bacterial lipopolysaccharides (LPS), has antibacterial activity.<ref>PMID:16637646</ref> <ref>PMID:18818205</ref> | + | [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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| | 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 4eyc" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lu, W]] | + | [[Category: Large Structures]] |
| - | [[Category: Pazgier, M]] | + | [[Category: Lu W]] |
| - | [[Category: Pozharski, E]] | + | [[Category: Pazgier M]] |
| - | [[Category: Toth, E]] | + | [[Category: Pozharski E]] |
| - | [[Category: Antimicrobial peptide]]
| + | [[Category: Toth E]] |
| - | [[Category: Cathelin-like domain]]
| + | |
| - | [[Category: Cystatin-like fold]]
| + | |
| - | [[Category: Pro-domain of human cathelicidin ll-37]]
| + | |
| - | [[Category: Unknown function]]
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| Structural highlights
Function
CAMP_HUMAN Binds to bacterial lipopolysaccharides (LPS), has antibacterial activity.[1] [2]
Publication Abstract from PubMed
Cathelicidins form a family of small host defense peptides distinct from another class of cationic antimicrobial peptides, the defensins. They are expressed as large precursor molecules with a highly conserved pro-domain known as the cathelin-like domain (CLD). CLDs have high degrees of sequence homology to cathelin, a protein isolated from pig leukocytes and belonging to the cystatin family of cysteine protease inhibitors. In this report, we describe for the first time the X-ray crystal structure of the human CLD (hCLD) of the sole human cathelicidin, LL-37. The structure of the hCLD, determined at 1.93 A resolution, shows the cystatin-like fold and is highly similar to the structure of the CLD of the pig cathelicidin, protegrin-3. We assayed the in vitro antibacterial activities of the hCLD, LL-37, and the precursor form, pro-cathelicidin (also known as hCAP18), and we found that the unprocessed protein inhibited the growth of Gram-negative bacteria with efficiencies comparable to that of the mature peptide, LL-37. In addition, the antibacterial activity of LL-37 was not inhibited by the hCLD intermolecularly, because exogenously added hCLD had no effect on the bactericidal activity of the mature peptide. The hCLD itself lacked antimicrobial function and did not inhibit the cysteine protease, cathepsin L. Our results contrast with previous reports of hCLD activity. A comparative structural analysis between the hCLD and the cysteine protease inhibitor stefin A showed why the hCLD is unable to function as an inhibitor of cysteine proteases. In this respect, the cystatin scaffold represents an ancestral structural platform from which proteins evolved divergently, with some losing inhibitory functions.
Structural and Functional Analysis of the Pro-Domain of Human Cathelicidin, LL-37.,Pazgier M, Ericksen B, Ling M, Toth E, Shi J, Li X, Galliher-Beckley A, Lan L, Zou G, Zhan C, Yuan W, Pozharski E, Lu W Biochemistry. 2013 Feb 21. PMID:23406372[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
- ↑ Pazgier M, Ericksen B, Ling M, Toth E, Shi J, Li X, Galliher-Beckley A, Lan L, Zou G, Zhan C, Yuan W, Pozharski E, Lu W. Structural and Functional Analysis of the Pro-Domain of Human Cathelicidin, LL-37. Biochemistry. 2013 Feb 21. PMID:23406372 doi:http://dx.doi.org/10.1021/bi301008r
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