4e83 - Revision history

OCA at 02:49, 21 November 2024

2024-11-21T02:49:18Z

← Older revision		Revision as of 02:49, 21 November 2024
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	== 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>		[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 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<ref>PMID:22573326</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4e83" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 14:55, 14 March 2024

2024-03-14T14:55:05Z

← Older revision		Revision as of 14:55, 14 March 2024
Line 10:		Line 10:
	== 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>		[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 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<ref>PMID:22573326</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4e83" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==

OCA at 08:21, 6 December 2023

2023-12-06T08:21:24Z

← Older revision		Revision as of 08:21, 6 December 2023
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	== Structural highlights ==		== Structural highlights ==
	<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>		<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" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</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='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='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'>[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>
	</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>		[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 ==

OCA at 06:56, 28 September 2022

2022-09-28T06:56:30Z

← Older revision		Revision as of 06:56, 28 September 2022
Line 3:		Line 3:
	<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='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='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='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='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'>[~~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 ==
Line 22:		Line 20:

	==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, M]]		[[Category: Pazgier M]]
	~~[[Category: Antimicrobial peptide]]~~
	~~[[Category: Antimicrobial protein]]~~
	~~[[Category: Beta-sheet structure]]~~
	~~[[Category: Leu29nle mutant]]~~
	~~[[Category: Paneth cell~~]]

OCA at 08:22, 27 March 2019

2019-03-27T08:22:45Z

← Older revision		Revision as of 08:22, 27 March 2019
Line 1:		Line 1:

	==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. 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>
Line 27:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Large Structures]]
	[[Category: Pazgier, M]]		[[Category: Pazgier, M]]
	[[Category: Antimicrobial peptide]]		[[Category: Antimicrobial peptide]]

OCA at 15:33, 5 August 2016

2016-08-05T15:33:22Z

← Older revision		Revision as of 15:33, 5 August 2016
Line 1:		Line 1:

	==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=''>
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	<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='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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1zmp\|1zmp]], [[4e82\|4e82]], [[4e86\|4e86]]</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'>[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://www.rcsb.org/pdb/explore.do?structureId=4e83 RCSB], [http://www.ebi.ac.uk/pdbsum/4e83 PDBsum]</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 ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 4e83" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 19:56, 25 December 2014

2014-12-25T19:56:42Z

← Older revision		Revision as of 19:56, 25 December 2014
Line 8:		Line 8:
	<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://www.rcsb.org/pdb/explore.do?structureId=4e83 RCSB], [http://www.ebi.ac.uk/pdbsum/4e83 PDBsum]</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://www.rcsb.org/pdb/explore.do?structureId=4e83 RCSB], [http://www.ebi.ac.uk/pdbsum/4e83 PDBsum]</span></td></tr>
	</table>		</table>
			== 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 11:47, 21 December 2014

2014-12-21T11:47:36Z

← Older revision		Revision as of 11:47, 21 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_4e83\| PDB=4e83 \| SCENE= }}~~		==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=''>
	~~{{ABSTRACT_PUBMED_22573326}}~~		== 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>
			</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>
			<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='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'>[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://www.rcsb.org/pdb/explore.do?structureId=4e83 RCSB], [http://www.ebi.ac.uk/pdbsum/4e83 PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== 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.

	~~==Function==~~		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<ref>PMID:22573326</ref>
	~~[[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>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[4e83]] is~~ a ~~2 chain structure. Full crystallographic information is available from [http://oca~~.~~weizmann~~.ac.~~il/oca-bin~~/~~ocashort?id=4E83 OCA].~~		</div>

	==~~Reference~~==		==See Also==
	~~<ref group~~=~~"xtra">PMID:022573326</ref>~~<references ~~group="xtra"~~/><~~references~~/>		*[[Defensin\|Defensin]]
	[[Category: Pazgier, M.]]		== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Pazgier, M]]
	[[Category: Antimicrobial peptide]]		[[Category: Antimicrobial peptide]]
	[[Category: Antimicrobial protein]]		[[Category: Antimicrobial protein]]

OCA at 10:05, 19 June 2013

2013-06-19T10:05:58Z

← Older revision		Revision as of 10:05, 19 June 2013
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	{{STRUCTURE_4e83\| PDB=4e83 \| SCENE= }}		{{STRUCTURE_4e83\| PDB=4e83 \| SCENE= }}
	===Crystal structure of human alpha-defensin 5, HD5 (Leu29NLe mutant)===		===Crystal structure of human alpha-defensin 5, HD5 (Leu29NLe mutant)===
	{{~~ABSTRACT_PUBMED_022573326~~}}		{{ABSTRACT_PUBMED_22573326}}

			==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>

	==About this Structure==		==About this Structure==
	[[4e83]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E83 OCA].		[[4e83]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E83 OCA].

	==~~See Also~~==		==Reference==
	*[[Defensin\|Defensin]]		<ref group="xtra">PMID:022573326</ref><references group="xtra"/><references/>
	[[Category: Pazgier, M.]]		[[Category: Pazgier, M.]]
	[[Category: Antimicrobial peptide]]		[[Category: Antimicrobial peptide]]

OCA at 10:10, 11 March 2013

2013-03-11T10:10:53Z

← Older revision		Revision as of 10:10, 11 March 2013
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	~~[[Image:4e83.jpg\|left\|200px]]~~

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_4e83", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_4e83\| PDB=4e83 \| SCENE= }}		{{STRUCTURE_4e83\| PDB=4e83 \| SCENE= }}

	===Crystal structure of human alpha-defensin 5, HD5 (Leu29NLe mutant)===		===Crystal structure of human alpha-defensin 5, HD5 (Leu29NLe mutant)===
			{{ABSTRACT_PUBMED_022573326}}

	==About this Structure==		==About this Structure==
	[[4e83]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E83 OCA].		[[4e83]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E83 OCA].

			==See Also==
			*[[Defensin\|Defensin]]
	[[Category: Pazgier, M.]]		[[Category: Pazgier, M.]]
	[[Category: Antimicrobial peptide]]		[[Category: Antimicrobial peptide]]