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| ==Human alpha-defensin 1 (multiple Arg->Lys mutant)== | | ==Human alpha-defensin 1 (multiple Arg->Lys mutant)== |
- | <StructureSection load='2pm4' size='340' side='right' caption='[[2pm4]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='2pm4' size='340' side='right'caption='[[2pm4]], [[Resolution|resolution]] 1.95Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[2pm4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PM4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PM4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2pm4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PM4 FirstGlance]. <br> |
- | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dfn|1dfn]], [[1zmi|1zmi]], [[1zmh|1zmh]], [[1zmk|1zmk]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1dfn|1dfn]], [[1zmi|1zmi]], [[1zmh|1zmh]], [[1zmk|1zmk]]</div></td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DEFA1, DEF1, DEFA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DEFA1, DEF1, DEFA2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2pm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pm4 OCA], [http://pdbe.org/2pm4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pm4 RCSB], [http://www.ebi.ac.uk/pdbsum/2pm4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2pm4 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=2pm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pm4 OCA], [https://pdbe.org/2pm4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pm4 RCSB], [https://www.ebi.ac.uk/pdbsum/2pm4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pm4 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
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| ==See Also== | | ==See Also== |
| *[[Defensin|Defensin]] | | *[[Defensin|Defensin]] |
| + | *[[Defensin 3D structures|Defensin 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
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| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Human]] |
| + | [[Category: Large Structures]] |
| [[Category: Lu, W]] | | [[Category: Lu, W]] |
| [[Category: Lubkowski, J]] | | [[Category: Lubkowski, J]] |
| Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human defensins are a family of small antimicrobial proteins found predominantly in leukocytes and epithelial cells that play important roles in the innate and adaptive immune defense against microbial infection. The most distinct molecular feature of defensins is cationicity, manifested by abundant Arg and/or Lys residues in their sequences. Sequence analysis indicates that Arg is strongly selected over Lys in alpha-defensins but not in beta-defensins. To understand this Arg/Lys disparity in defensins, we chemically synthesized human alpha-defensin 1 (HNP1) and several HNP1 analogs where three Arg residues were replaced by each of the following six alpha-amino acids: Lys, ornithine (Orn), diaminobutyric acid (Dab), diaminopropionic acid (Dap), N,N-dimethyl-Lys ((diMe)Lys), and homo-Arg ((homo)Arg). In addition, we prepared human beta-defensin 1 (hBD1) and (Lys-->Arg)hBD1 in which all four Lys residues were substituted for Arg. Bactericidal activity assays revealed the following. 1) Arg-containing HNP1 and (Lys-->Arg)hBD1 are functionally better than Lys-HNP1 and hBD1, respectively; the difference between Arg and Lys is more evident in the alpha-defensin than in the beta-defensin and is more evident at low salt concentrations than at high salt concentrations. 2) For HNP1, the Arg/Lys disparity is much more pronounced with Staphylococcus aureus than with Escherichia coli, and the Arg-rich HNP1 kills bacteria faster than its Lys-rich analog. 3) Arg and Lys appear to have optimal chain lengths for bacterial killing as shortening Lys or lengthening Arg in HNP1 invariably becomes functionally deleterious. Our findings provide insights into the Arg/Lys disparity in defensins, and shed light on the cationicity of defensins with respect to their antimicrobial activity and specificity.
Toward understanding the cationicity of defensins. Arg and Lys versus their noncoded analogs.,Zou G, de Leeuw E, Li C, Pazgier M, Li C, Zeng P, Lu WY, Lubkowski J, Lu W J Biol Chem. 2007 Jul 6;282(27):19653-65. Epub 2007 Apr 23. PMID:17452329[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zou G, de Leeuw E, Li C, Pazgier M, Li C, Zeng P, Lu WY, Lubkowski J, Lu W. Toward understanding the cationicity of defensins. Arg and Lys versus their noncoded analogs. J Biol Chem. 2007 Jul 6;282(27):19653-65. Epub 2007 Apr 23. PMID:17452329 doi:10.1074/jbc.M611003200
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