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4e86

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Revision as of 04:09, 5 August 2016

Crystal structure of human alpha-defensin 5, HD5 (Leu29Aba mutant)

Structural highlights

4e86 is a 9 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	1zmp, 4e82, 4e83
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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.

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
↑ Rajabi M, Ericksen B, Wu X, de Leeuw E, Zhao L, Pazgier M, Lu W. Functional determinants of human enteric alpha-defensin HD5: crucial role for hydrophobicity at dimer interface. J Biol Chem. 2012 Jun 22;287(26):21615-27. Epub 2012 May 9. PMID:22573326 doi:10.1074/jbc.M112.367995

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4e86"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human alpha-defensin 5, HD5 (Leu29Aba mutant)==
 <StructureSection load='4e86' size='340' side='right' caption='[[4e86]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zmp|1zmp]], [[4e82|4e82]], [[4e83|4e83]]</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=4e86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e86 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e86 RCSB], [http://www.ebi.ac.uk/pdbsum/4e86 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=4e86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e86 OCA], [http://pdbe.org/4e86 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e86 RCSB], [http://www.ebi.ac.uk/pdbsum/4e86 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e86 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4e86" style="background-color:#fffaf0;"></div>
 ==See Also==

4e86

From Proteopedia

Revision as of 04:09, 5 August 2016

Crystal structure of human alpha-defensin 5, HD5 (Leu29Aba mutant)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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