2poa: Difference between revisions

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-[[Image:2poa.png|left|200px]]
+==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 [http://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2POA FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2poa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2poa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2poa RCSB], [http://www.ebi.ac.uk/pdbsum/2poa PDBsum]</span></td></tr>
+<table>
+== 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/chain_selection.php?pdb_ID=2ata 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.
-{{STRUCTURE_2poa|  PDB=2poa  |  SCENE=  }}
+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>
-===Schistosoma mansoni Sm14 Fatty Acid-Binding Protein: improvement of protein stability by substitution of the single Cys62 residue===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_19150418}}
-==About this Structure==
-[[2poa]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2POA OCA].
 ==See Also==
 *[[Fatty acid-binding protein|Fatty acid-binding protein]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:019150418</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Schistosoma mansoni]]
 [[Category: Ho, P L.]]