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| | ==Crystal structure of human alpha-defensin 5, HD5 (Thr7Arg Glu21Arg mutant)== | | ==Crystal structure of human alpha-defensin 5, HD5 (Thr7Arg Glu21Arg mutant)== |
| - | <StructureSection load='4rbw' size='340' side='right' caption='[[4rbw]], [[Resolution|resolution]] 1.50Å' scene=''> | + | <StructureSection load='4rbw' size='340' side='right'caption='[[4rbw]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4rbw]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RBW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RBW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4rbw]] is a 4 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=4RBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RBW 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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zmp|1zmp]], [[4e82|4e82]], [[4e83|4e83]], [[4e86|4e86]], [[4rbx|4rbx]]</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=SO4:SULFATE+ION'>SO4</scene></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=4rbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rbw OCA], [http://pdbe.org/4rbw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rbw RCSB], [http://www.ebi.ac.uk/pdbsum/4rbw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rbw ProSAT]</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=4rbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rbw OCA], [https://pdbe.org/4rbw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rbw RCSB], [https://www.ebi.ac.uk/pdbsum/4rbw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rbw 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: Gohain, N]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Pazgier, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Tolbert, W D]] | + | [[Category: Gohain N]] |
| - | [[Category: Antimicrobial peptide]] | + | [[Category: Pazgier M]] |
| - | [[Category: Antimicrobial protein]] | + | [[Category: Tolbert WD]] |
| - | [[Category: Beta-sheet]]
| + | |
| - | [[Category: Human alpha-defensin]]
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| - | [[Category: Mutant t7r e21r-hd5]]
| + | |
| - | [[Category: Paneth cells defensin]]
| + | |
| 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 defensin 5 (HD5) is a broad-spectrum antibacterial peptide with a C-terminal active region. To promote the development of this peptide into an antibiotic, we initially substituted Glu21 with Arg because it is an electronegative residue located around the active region. Although detrimental to dimer formation, the E21R substitution markedly enhanced the antibacterial activity of HD5 and increased its ability to penetrate cell membranes, demonstrating that increasing the electropositive charge compensated for the effect of dimer disruption. Subsequently, a partial Arg scanning mutagenesis was performed, and Thr7 was selected for replacement with Arg to further strengthen the antibacterial activity. The newly designed peptide, T7E21R-HD5, exhibited potent antibacterial activity, even in saline and serum solutions. In contrast to monomeric E21R-HD5, T7E21R-HD5 assembled into an atypical dimer with parallel beta strands, thus expanding the role of increasing electropositive charge in bactericidal activity and providing a useful guide for further defensin-derived antibiotic design.
Design of a potent antibiotic peptide based on the active region of human defensin 5.,Wang C, Shen M, Gohain N, Tolbert WD, Chen F, Zhang N, Yang K, Wang A, Su Y, Cheng T, Zhao J, Pazgier M, Wang J J Med Chem. 2015 Apr 9;58(7):3083-93. doi: 10.1021/jm501824a. Epub 2015 Mar 20. PMID:25782105[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
- ↑ Wang C, Shen M, Gohain N, Tolbert WD, Chen F, Zhang N, Yang K, Wang A, Su Y, Cheng T, Zhao J, Pazgier M, Wang J. Design of a potent antibiotic peptide based on the active region of human defensin 5. J Med Chem. 2015 Apr 9;58(7):3083-93. doi: 10.1021/jm501824a. Epub 2015 Mar 20. PMID:25782105 doi:http://dx.doi.org/10.1021/jm501824a
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