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| | ==Crystal structure of human alpha-defensin 5, HD5 (Leu29NLe mutant)== | | ==Crystal structure of human alpha-defensin 5, HD5 (Leu29NLe mutant)== |
| - | <StructureSection load='4e83' size='340' side='right' caption='[[4e83]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4e83' size='340' side='right'caption='[[4e83]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4e83]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E83 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E83 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4e83]] 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=4E83 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E83 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zmp|1zmp]], [[4e82|4e82]], [[4e86|4e86]]</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=4e83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e83 OCA], [https://pdbe.org/4e83 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e83 RCSB], [https://www.ebi.ac.uk/pdbsum/4e83 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e83 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=4e83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e83 OCA], [http://pdbe.org/4e83 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e83 RCSB], [http://www.ebi.ac.uk/pdbsum/4e83 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e83 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DEF5_HUMAN DEF5_HUMAN]] Has antimicrobial activity against Gram-negative and Gram-positive bacteria. Defensins are thought to kill microbes by permeabilizing their plasma membrane. All DEFA5 peptides exert antimicrobial activities, but their potency is affected by peptide processing.<ref>PMID:12021776</ref> <ref>PMID:15616305</ref> <ref>PMID:17088326</ref> | + | [https://www.uniprot.org/uniprot/DEF5_HUMAN DEF5_HUMAN] Has antimicrobial activity against Gram-negative and Gram-positive bacteria. Defensins are thought to kill microbes by permeabilizing their plasma membrane. All DEFA5 peptides exert antimicrobial activities, but their potency is affected by peptide processing.<ref>PMID:12021776</ref> <ref>PMID:15616305</ref> <ref>PMID:17088326</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Defensin|Defensin]] | + | *[[Defensin 3D structures|Defensin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pazgier, M]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Antimicrobial peptide]] | + | [[Category: Large Structures]] |
| - | [[Category: Antimicrobial protein]] | + | [[Category: Pazgier M]] |
| - | [[Category: Beta-sheet structure]]
| + | |
| - | [[Category: Leu29nle mutant]]
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| - | [[Category: Paneth cell]]
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| Structural highlights
Function
DEF5_HUMAN Has antimicrobial activity against Gram-negative and Gram-positive bacteria. Defensins are thought to kill microbes by permeabilizing their plasma membrane. All DEFA5 peptides exert antimicrobial activities, but their potency is affected by peptide processing.[1] [2] [3]
Publication Abstract from PubMed
Human alpha-defensins are cationic peptides that self-associate into dimers and higher-order oligomers. They bind protein toxins, such as anthrax lethal factor (LF), and kill bacteria, including Escherichia coli and Staphylococcus aureus, among other functions. There are six members of the human alpha-defensin family: four human neutrophil peptides, including HNP1, and two enteric human defensins, including HD5. We subjected HD5 to comprehensive alanine scanning mutagenesis. We then assayed LF binding by surface plasmon resonance, LF activity by enzyme kinetic inhibition, and antibacterial activity by the virtual colony count assay. Most mutations could be tolerated, resulting in activity comparable with that of wild type HD5. However, the L29A mutation decimated LF binding and bactericidal activity against Escherichia coli and Staphylococcus aureus. A series of unnatural aliphatic and aromatic substitutions at position 29, including aminobutyric acid (Abu) and norleucine (Nle) correlated hydrophobicity with HD5 function. The crystal structure of L29Abu-HD5 depicted decreased hydrophobic contacts at the dimer interface, whereas the Nle-29-HD5 crystal structure depicted a novel mode of dimerization with parallel beta strands. The effect of mutating Leu(29) is similar to that of a C-terminal hydrophobic residue of HNP1, Trp(26). In addition, in order to further clarify the role of dimerization in HD5 function, an obligate monomer was generated by N-methylation of the Glu(21) residue, decreasing LF binding and antibacterial activity against S. aureus. These results further characterize the dimer interface of the alpha-defensins, revealing a crucial role of hydrophobicity-mediated dimerization.
Functional determinants of human enteric alpha-defensin HD5: crucial role for hydrophobicity at dimer interface.,Rajabi M, Ericksen B, Wu X, de Leeuw E, Zhao L, Pazgier M, Lu W J Biol Chem. 2012 Jun 22;287(26):21615-27. Epub 2012 May 9. PMID:22573326[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, Yadav SP, Crabb JW, Ganz T, Bevins CL. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol. 2002 Jun;3(6):583-90. Epub 2002 May 20. PMID:12021776 doi:10.1038/ni797
- ↑ Ericksen B, Wu Z, Lu W, Lehrer RI. Antibacterial activity and specificity of the six human {alpha}-defensins. Antimicrob Agents Chemother. 2005 Jan;49(1):269-75. PMID:15616305 doi:10.1128/AAC.49.1.269-275.2005
- ↑ Szyk A, Wu Z, Tucker K, Yang D, Lu W, Lubkowski J. Crystal structures of human alpha-defensins HNP4, HD5, and HD6. Protein Sci. 2006 Dec;15(12):2749-60. Epub 2006 Nov 6. PMID:17088326 doi:ps.062336606
- ↑ Rajabi M, Ericksen B, Wu X, de Leeuw E, Zhao L, Pazgier M, Lu W. Functional determinants of human enteric alpha-defensin HD5: crucial role for hydrophobicity at dimer interface. J Biol Chem. 2012 Jun 22;287(26):21615-27. Epub 2012 May 9. PMID:22573326 doi:10.1074/jbc.M112.367995
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