4lb7: Difference between revisions
New page: '''Unreleased structure''' The entry 4lb7 is ON HOLD Authors: Zhao, L., Tolbert, W.D., Erickson, B., Zhan, C., Wu, X., Yuan, W., Li, X., Pazgier, M., Lu, W. Description: Crystal struct... |
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The | ==Crystal structure of human alpha-defensin 1 (HNP1) Y16A/I20A/L25A/F28A mutant.== | ||
<StructureSection load='4lb7' size='340' side='right'caption='[[4lb7]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4lb7]] 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=4LB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LB7 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]] 1.902Å</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=4lb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lb7 OCA], [https://pdbe.org/4lb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lb7 RCSB], [https://www.ebi.ac.uk/pdbsum/4lb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lb7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DEF1_HUMAN DEF1_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
HNP1 is a human alpha defensin that forms dimers and multimers governed by hydrophobic residues, including Tyr(16), Ile(20), Leu(25), and Phe(28). Previously, alanine scanning mutagenesis identified each of these residues and other hydrophobic residues as important for function. Here we report further structural and functional studies of residues shown to interact with one another across oligomeric interfaces: I20A-HNP1 and L25A-HNP1, plus the double alanine mutants I20A/L25A-HNP1 and Y16A/F28A-HNP1, and the quadruple alanine mutant Y16A/I20A/L25A/F28A-HNP1. We tested binding to HIV-1 gp120 and HNP1 by surface plasmon resonance, binding to HIV-1 gp41 and HNP1 by fluorescence polarization, inhibition of anthrax lethal factor, and antibacterial activity using the virtual colony count assay. Similar to the previously described single mutant W26A-HNP1, the quadruple mutant displayed the least activity in all functional assays, followed by the double mutant Y16A/F28A-HNP1. The effects of the L25A and I20A single mutations were milder than the double mutant I20A/L25A-HNP1. Crystallographic studies confirmed the correct folding and disulfide pairing, and depicted an array of dimeric and tetrameric structures. These results indicate that side chain hydrophobicity is the critical factor that determines activity at these positions. | |||
Single, Double and Quadruple Alanine Substitutions at Oligomeric Interfaces Identify Hydrophobicity as the Key Determinant of Human Neutrophil Alpha Defensin HNP1 Function.,Zhao L, Tolbert WD, Ericksen B, Zhan C, Wu X, Yuan W, Li X, Pazgier M, Lu W PLoS One. 2013 Nov 13;8(11):e78937. doi: 10.1371/journal.pone.0078937. PMID:24236072<ref>PMID:24236072</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4lb7" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Defensin 3D structures|Defensin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Pazgier M]] | |||
[[Category: Tolbert WD]] | |||
[[Category: Wu X]] | |||
Latest revision as of 19:16, 20 September 2023
Crystal structure of human alpha-defensin 1 (HNP1) Y16A/I20A/L25A/F28A mutant.Crystal structure of human alpha-defensin 1 (HNP1) Y16A/I20A/L25A/F28A mutant.
Structural highlights
FunctionPublication Abstract from PubMedHNP1 is a human alpha defensin that forms dimers and multimers governed by hydrophobic residues, including Tyr(16), Ile(20), Leu(25), and Phe(28). Previously, alanine scanning mutagenesis identified each of these residues and other hydrophobic residues as important for function. Here we report further structural and functional studies of residues shown to interact with one another across oligomeric interfaces: I20A-HNP1 and L25A-HNP1, plus the double alanine mutants I20A/L25A-HNP1 and Y16A/F28A-HNP1, and the quadruple alanine mutant Y16A/I20A/L25A/F28A-HNP1. We tested binding to HIV-1 gp120 and HNP1 by surface plasmon resonance, binding to HIV-1 gp41 and HNP1 by fluorescence polarization, inhibition of anthrax lethal factor, and antibacterial activity using the virtual colony count assay. Similar to the previously described single mutant W26A-HNP1, the quadruple mutant displayed the least activity in all functional assays, followed by the double mutant Y16A/F28A-HNP1. The effects of the L25A and I20A single mutations were milder than the double mutant I20A/L25A-HNP1. Crystallographic studies confirmed the correct folding and disulfide pairing, and depicted an array of dimeric and tetrameric structures. These results indicate that side chain hydrophobicity is the critical factor that determines activity at these positions. Single, Double and Quadruple Alanine Substitutions at Oligomeric Interfaces Identify Hydrophobicity as the Key Determinant of Human Neutrophil Alpha Defensin HNP1 Function.,Zhao L, Tolbert WD, Ericksen B, Zhan C, Wu X, Yuan W, Li X, Pazgier M, Lu W PLoS One. 2013 Nov 13;8(11):e78937. doi: 10.1371/journal.pone.0078937. PMID:24236072[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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