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2pm4

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Human alpha-defensin 1 (multiple Arg->Lys mutant)

Structural highlights

2pm4 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.95Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DEF3_HUMAN Defensin 2 and defensin 3 have antibiotic, fungicide and antiviral activities. Has antimicrobial activity against Gram-negative and Gram-positive bacteria. Defensins are thought to kill microbes by permeabilizing their plasma membrane.^[1] ^[2] ^[3] ^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ Hill CP, Yee J, Selsted ME, Eisenberg D. Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science. 1991 Mar 22;251(5000):1481-5. PMID:2006422
↑ Xie C, Prahl A, Ericksen B, Wu Z, Zeng P, Li X, Lu WY, Lubkowski J, Lu W. Reconstruction of the conserved beta-bulge in mammalian defensins using D-amino acids. J Biol Chem. 2005 Sep 23;280(38):32921-9. Epub 2005 May 13. PMID:15894545 doi:M503084200
↑ 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
↑ 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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2pm4"

Categories: Homo sapiens | Large Structures | Lu W | Lubkowski J | Pazgier M

@@ Line 1: / Line 1: @@
 ==Human alpha-defensin 1 (multiple Arg->Lys mutant)==
-<StructureSection load='2pm4' size='340' side='right' caption='[[2pm4]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
+<StructureSection load='2pm4' size='340' side='right'caption='[[2pm4]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == 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/Homo_sapiens Homo sapiens]. 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</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='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>
-<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]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/DEF3_HUMAN DEF3_HUMAN] Defensin 2 and defensin 3 have antibiotic, fungicide and antiviral activities. Has antimicrobial activity against Gram-negative and Gram-positive bacteria. Defensins are thought to kill microbes by permeabilizing their plasma membrane.<ref>PMID:15616305</ref> <ref>PMID:2006422</ref> <ref>PMID:15894545</ref> <ref>PMID:17452329</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pm/2pm4_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pm/2pm4_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2pm4 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 29: / Line 31: @@
 ==See Also==
 *[[Defensin|Defensin]]
+*[[Defensin 3D structures|Defensin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Lu, W]]
+[[Category: Large Structures]]
-[[Category: Lubkowski, J]]
+[[Category: Lu W]]
-[[Category: Pazgier, M]]
+[[Category: Lubkowski J]]
-[[Category: Antimicrobial]]
+[[Category: Pazgier M]]
-[[Category: Antimicrobial protein]]
-[[Category: Defensin]]
-[[Category: Mutant]]

2pm4

From Proteopedia

Current revision

Human alpha-defensin 1 (multiple Arg->Lys mutant)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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