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| | ==NMR solution structure of the Dermaseptin antimicrobial peptide analog NC12-K4S4(1-13)a== | | ==NMR solution structure of the Dermaseptin antimicrobial peptide analog NC12-K4S4(1-13)a== |
| - | <StructureSection load='2dcx' size='340' side='right'caption='[[2dcx]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='2dcx' size='340' side='right'caption='[[2dcx]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2dcx]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DCX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2dcx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Phyllomedusa_sauvagii Phyllomedusa sauvagii]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DCX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DOA:12-AMINO-DODECANOIC+ACID'>DOA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DOA:12-AMINO-DODECANOIC+ACID'>DOA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2dd6|2dd6]]</div></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=2dcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dcx OCA], [https://pdbe.org/2dcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dcx RCSB], [https://www.ebi.ac.uk/pdbsum/2dcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dcx 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=2dcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dcx OCA], [https://pdbe.org/2dcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dcx RCSB], [https://www.ebi.ac.uk/pdbsum/2dcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dcx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DMS4_PHYSA DMS4_PHYSA]] Possesses a potent antimicrobial activity against Gram-negative and Gram-positive bacteria, fungi, protozoa, and the enveloped herpes simplex virus type 1. Probably acts by disturbing membrane functions with its amphipathic structure. Binds to healthy erythrocytes (this binding is receptor independent), and has strong hemolytic activity. Does not bind to P.falciparum infected erythrocytes, but accumulates within the parasite. Kills the parasite, and only at high concentrations has a hemolytic activity on the host cell.<ref>PMID:8306981</ref> <ref>PMID:9395500</ref>
| + | [https://www.uniprot.org/uniprot/DRS4_PHYSA DRS4_PHYSA] Potent antimicrobial peptide with activity against bacteria and protozoa (By similarity). Also has activity against fungi (PubMed:8306981). Also shows activity against enveloped herpes simplex virus type 1 (PubMed:11782932). Probably acts by disturbing membrane functions with its amphipathic structure (Probable). Binds to healthy erythrocytes (this binding is receptor independent), and has strong hemolytic activity (PubMed:9395500). Does not bind to P.falciparum infected erythrocytes, but accumulates within the parasite (PubMed:9395500). Kills the parasite, and only at high concentrations has a hemolytic activity on the host cell (PubMed:9395500). In vitro, shows high spermicidal activities (PubMed:16307969).[UniProtKB:P24302]<ref>PMID:11782932</ref> <ref>PMID:16307969</ref> <ref>PMID:8306981</ref> <ref>PMID:9395500</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fish, A]] | + | [[Category: Phyllomedusa sauvagii]] |
| - | [[Category: Mor, A]] | + | [[Category: Fish A]] |
| - | [[Category: Rotem, S]] | + | [[Category: Mor A]] |
| - | [[Category: Shalev, D E]] | + | [[Category: Rotem S]] |
| - | [[Category: Alpha-helix]] | + | [[Category: Shalev DE]] |
| - | [[Category: Antimicrobial protein]]
| + | |
| Structural highlights
Function
DRS4_PHYSA Potent antimicrobial peptide with activity against bacteria and protozoa (By similarity). Also has activity against fungi (PubMed:8306981). Also shows activity against enveloped herpes simplex virus type 1 (PubMed:11782932). Probably acts by disturbing membrane functions with its amphipathic structure (Probable). Binds to healthy erythrocytes (this binding is receptor independent), and has strong hemolytic activity (PubMed:9395500). Does not bind to P.falciparum infected erythrocytes, but accumulates within the parasite (PubMed:9395500). Kills the parasite, and only at high concentrations has a hemolytic activity on the host cell (PubMed:9395500). In vitro, shows high spermicidal activities (PubMed:16307969).[UniProtKB:P24302][1] [2] [3] [4]
Publication Abstract from PubMed
Acyl conjugation to antimicrobial peptides is known to enhance antimicrobial properties. Here, we investigated the consequences of aminolauryl (NC(12)) conjugation to the dermaseptin derivative K(4)-S4-(1-13) (P) on binding properties to bilayer models mimicking bacterial plasma membrane, which is often cited as the ultimate site of action. Isothermal titration calorimetry revealed that acylation was responsible for enhancing the binding affinity of NC(12)-P compared with P (K = 13 x 10(5) and 1.5 x 10(5) m(-1), respectively). Surface plasmon resonance measurements confirmed the isothermal titration calorimetry results (K(app) = 12.6 x 10(5) and 1.53 x 10(5) m(-1), respectively) and further indicated that enhanced adhesion affinity (K(adhesion) = 3 x 10(5) and 1 x 10(5) m(-1), respectively) was coupled to enhanced tendency to insert within the bilayer (K(insertion) = 4.5 and 1.5, respectively). To gain insight into the molecular basis for these observations, we investigated the three-dimensional structures in the presence of dodecylphosphocholine using NMR. The ensemble of NMR-calculated structures (backbone root mean square deviation <0.6 A) showed that the acyl moiety was responsible for a significant molecular reorganization, possibly affecting the electrostatic potential distribution in NC(12)-P relative to that of P. The combined data present compelling evidence in support of the hypothesis that N-acylation affects antimicrobial properties by modifying the secondary structure of the peptide in a manner that facilitates contact with the membrane and consequently increases its disruption.
Consequences of N-acylation on structure and membrane binding properties of dermaseptin derivative K4-S4-(1-13).,Shalev DE, Rotem S, Fish A, Mor A J Biol Chem. 2006 Apr 7;281(14):9432-8. Epub 2005 Dec 30. PMID:16407175[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Belaid A, Aouni M, Khelifa R, Trabelsi A, Jemmali M, Hani K. In vitro antiviral activity of dermaseptins against herpes simplex virus type 1. J Med Virol. 2002 Feb;66(2):229-34. PMID:11782932 doi:10.1002/jmv.2134
- ↑ Zairi A, Belaïd A, Gahbiche A, Hani K. Spermicidal activity of dermaseptins. Contraception. 2005 Dec;72(6):447-53. PMID:16307969 doi:10.1016/j.contraception.2005.06.055
- ↑ Mor A, Nicolas P. Isolation and structure of novel defensive peptides from frog skin. Eur J Biochem. 1994 Jan 15;219(1-2):145-54. PMID:8306981
- ↑ Ghosh JK, Shaool D, Guillaud P, Ciceron L, Mazier D, Kustanovich I, Shai Y, Mor A. Selective cytotoxicity of dermaseptin S3 toward intraerythrocytic Plasmodium falciparum and the underlying molecular basis. J Biol Chem. 1997 Dec 12;272(50):31609-16. PMID:9395500
- ↑ Shalev DE, Rotem S, Fish A, Mor A. Consequences of N-acylation on structure and membrane binding properties of dermaseptin derivative K4-S4-(1-13). J Biol Chem. 2006 Apr 7;281(14):9432-8. Epub 2005 Dec 30. PMID:16407175 doi:M513051200
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