4e86: Difference between revisions
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<StructureSection load='4e86' size='340' side='right'caption='[[4e86]], [[Resolution|resolution]] 2.75Å' scene=''> | <StructureSection load='4e86' size='340' side='right'caption='[[4e86]], [[Resolution|resolution]] 2.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4e86]] is a 9 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E86 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4e86]] is a 9 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=4E86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E86 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=4e86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e86 OCA], [https://pdbe.org/4e86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e86 RCSB], [https://www.ebi.ac.uk/pdbsum/4e86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e86 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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;"> | <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: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Pazgier | [[Category: Pazgier M]] | ||
[[Category: Wu | [[Category: Wu X]] | ||
Revision as of 09:56, 28 September 2022
Crystal structure of human alpha-defensin 5, HD5 (Leu29Aba mutant)Crystal structure of human alpha-defensin 5, HD5 (Leu29Aba mutant)
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 PubMedHuman 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 AlsoReferences
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