2e3e: Difference between revisions
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< | ==NMR structure of DEF-BBB, a mutant of anopheles defensin DEF-AAA== | ||
<StructureSection load='2e3e' size='340' side='right'caption='[[2e3e]]' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2e3e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Anopheles_gambiae Anopheles gambiae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E3E FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 9 models</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=2e3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e3e OCA], [https://pdbe.org/2e3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e3e RCSB], [https://www.ebi.ac.uk/pdbsum/2e3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e3e ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DEFI_ANOGA DEFI_ANOGA] Responsible for the anti Gram-positive activity of immune hemolymph (By similarity). | |||
== 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/e3/2e3e_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=2e3e ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In an attempt to increase the antimicrobial activity of the insect defensin from Anopheles gambiae, which is active against Staphylococcus aureus at low concentration, hybrid defensins were designed by combining conserved sequence regions and variable regions of insect defensins. Their activity against S. aureus strains sensitive and resistant to conventional antibiotics was evaluated, and the toxicity of the most active molecules was tested. The three-dimensional structure of Anopheles gambiae defensin and five hybrids were determined by NMR and molecular modelling. This strategy led to the design of two chimeric defensins with increased activity compared with the native molecule, but one of them appears to be toxic to mice at a rather low concentration. The structure of the CS alphabeta motif, which is a characteristic of insect defensin, is sensitive to sequence modifications, in particular in the N-terminal loop. The existence of the CS alphabeta is most probably a prerequisite for the stability and the activity of the molecule, but is not sufficient by itself since the hybrid displaying the best defined structure is not active against the tested strains. The analysis of the structure, in relation with the activity and the toxicity data, underlines the importance of turns and of the N-terminal loop. Residues located in the turns contributing to the preservation of positive electrostatic areas at the surface of the molecules seem particularly important for the activity of the molecule, while residues involved in the N-terminal loop are both involved in the modulation of the activity and the toxicity of the molecule. | |||
Rational design of peptides active against the gram positive bacteria Staphylococcus aureus.,Landon C, Barbault F, Legrain M, Guenneugues M, Vovelle F Proteins. 2008 Jul;72(1):229-39. PMID:18214975<ref>PMID:18214975</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2e3e" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Defensin 3D structures|Defensin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Anopheles gambiae]] | [[Category: Anopheles gambiae]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Barbault | [[Category: Barbault F]] | ||
[[Category: Landon | [[Category: Landon C]] | ||
[[Category: Vovelle | [[Category: Vovelle F]] | ||
Latest revision as of 10:56, 30 October 2024
NMR structure of DEF-BBB, a mutant of anopheles defensin DEF-AAANMR structure of DEF-BBB, a mutant of anopheles defensin DEF-AAA
Structural highlights
FunctionDEFI_ANOGA Responsible for the anti Gram-positive activity of immune hemolymph (By similarity). 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 PubMedIn an attempt to increase the antimicrobial activity of the insect defensin from Anopheles gambiae, which is active against Staphylococcus aureus at low concentration, hybrid defensins were designed by combining conserved sequence regions and variable regions of insect defensins. Their activity against S. aureus strains sensitive and resistant to conventional antibiotics was evaluated, and the toxicity of the most active molecules was tested. The three-dimensional structure of Anopheles gambiae defensin and five hybrids were determined by NMR and molecular modelling. This strategy led to the design of two chimeric defensins with increased activity compared with the native molecule, but one of them appears to be toxic to mice at a rather low concentration. The structure of the CS alphabeta motif, which is a characteristic of insect defensin, is sensitive to sequence modifications, in particular in the N-terminal loop. The existence of the CS alphabeta is most probably a prerequisite for the stability and the activity of the molecule, but is not sufficient by itself since the hybrid displaying the best defined structure is not active against the tested strains. The analysis of the structure, in relation with the activity and the toxicity data, underlines the importance of turns and of the N-terminal loop. Residues located in the turns contributing to the preservation of positive electrostatic areas at the surface of the molecules seem particularly important for the activity of the molecule, while residues involved in the N-terminal loop are both involved in the modulation of the activity and the toxicity of the molecule. Rational design of peptides active against the gram positive bacteria Staphylococcus aureus.,Landon C, Barbault F, Legrain M, Guenneugues M, Vovelle F Proteins. 2008 Jul;72(1):229-39. PMID:18214975[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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