2poa: Difference between revisions
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< | ==Schistosoma mansoni Sm14 Fatty Acid-Binding Protein: improvement of protein stability by substitution of the single Cys62 residue== | ||
<StructureSection load='2poa' size='340' side='right'caption='[[2poa]], [[NMR_Ensembles_of_Models | 17 NMR models]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2poa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Blood_fluke Blood fluke]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2POA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2POA FirstGlance]. <br> | |||
</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=2poa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2poa OCA], [https://pdbe.org/2poa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2poa RCSB], [https://www.ebi.ac.uk/pdbsum/2poa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2poa ProSAT]</span></td></tr> | |||
-- | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/FABP_SCHMA FABP_SCHMA]] May play a role in the transport of fatty acids. Binds various fatty acids, such as arachidonic, oleic, palmitic and linolenic acid (in vitro). | |||
== 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/po/2poa_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/main_output.php?pdb_ID=2poa ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Schistosoma mansoni fatty acid binding protein (FABP), Sm14, is a vaccine candidate against, S. mansoni and F. hepatica. Previously, we demonstrated the importance of a correct fold to achieve protection in immunized animals after cercariae challenge [[10]. C.R.R. Ramos, R.C.R. Figueredo, T.A. Pertinhez, M.M. Vilar, A.L.T.O. Nascimento, M. Tendler, I. Raw, A. Spisni, P.L. Ho, Gene structure and M20T polymorphism of the Schistosoma mansoni Sm14 fatty acid-binding protein: structural, functional and immunoprotection analysis. J. Biol. Chem. 278 (2003) 12745-12751.]. Here we show that the reduction of vaccine efficacy over time is due to protein dimerization and subsequent aggregation. We produced the mutants Sm14-M20(C62S) and Sm14-M20(C62V) that, as expected, did not dimerize in SDS-PAGE. Molecular dynamics calculations and unfolding experiments highlighted a higher structural stability of these mutants with respect to the wild-type. In addition, we found that the mutated proteins, after thermal denaturation, refolded to their active native molecular architecture as proved by the recovery of the fatty acid binding ability. Sm14-M20(C62V) turned out to be the more stable form over time, providing the basis to determine the first 3D solution structure of a Sm14 protein in its apo-form. Overall, Sm14-M20(C62V) possesses an improved structural stability over time, an essential feature to preserve its immunization capability and, in experimentally immunized animals, it exhibits a protection effect against S. mansoni cercariae infections comparable to the one obtained with the wild-type protein. These facts indicate this protein as a good lead molecule for large-scale production and for developing an effective Sm14 based anti-helminthes vaccine. | |||
Stability improvement of the fatty acid binding protein Sm14 from S. mansoni by Cys replacement: structural and functional characterization of a vaccine candidate.,Ramos CR, Spisni A, Oyama S Jr, Sforca ML, Ramos HR, Vilar MM, Alves AC, Figueredo RC, Tendler M, Zanchin NI, Pertinhez TA, Ho PL Biochim Biophys Acta. 2009 Apr;1794(4):655-62. Epub 2008 Dec 25. PMID:19150418<ref>PMID:19150418</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2poa" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Fatty acid-binding protein 3D structures|Fatty acid-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Blood fluke]] | ||
[[Category: Large Structures]] | |||
[[Category: Ho, P L]] | |||
== | [[Category: Oyama, S]] | ||
< | [[Category: Pertinhez, T A]] | ||
[[Category: | [[Category: Ramos, C R.R]] | ||
[[Category: Ho, P L | [[Category: Sforca, M L]] | ||
[[Category: | [[Category: Spisni, A]] | ||
[[Category: Pertinhez, T A | |||
[[Category: Ramos, C R.R | |||
[[Category: Sforca, M L | |||
[[Category: Spisni, A | |||
[[Category: Fatty acid binding protein]] | [[Category: Fatty acid binding protein]] | ||
[[Category: Lipid binding protein]] | [[Category: Lipid binding protein]] | ||
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[[Category: Site directed mutagenesis]] | [[Category: Site directed mutagenesis]] | ||
[[Category: Vaccine antigen]] | [[Category: Vaccine antigen]] | ||