4rbx: Difference between revisions
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==Crystal structure of human alpha-defensin 5, HD5 (Glu21Arg mutant)== | |||
<StructureSection load='4rbx' size='340' side='right'caption='[[4rbx]], [[Resolution|resolution]] 1.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4rbx]] is a 1 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=4RBX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RBX FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=4rbx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rbx OCA], [https://pdbe.org/4rbx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rbx RCSB], [https://www.ebi.ac.uk/pdbsum/4rbx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rbx ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== 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<ref>PMID:25782105</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4rbx" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Defensin 3D structures|Defensin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Gohain N]] | |||
[[Category: Pazgier M]] | |||
[[Category: Tolbert WD]] | |||
Latest revision as of 20:47, 20 September 2023
Crystal structure of human alpha-defensin 5, HD5 (Glu21Arg mutant)Crystal structure of human alpha-defensin 5, HD5 (Glu21Arg mutant)
Structural highlights
FunctionDEF5_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 PubMedHuman 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 AlsoReferences
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