2poa: Difference between revisions
No edit summary |
No edit summary |
||
| Line 2: | Line 2: | ||
<StructureSection load='2poa' size='340' side='right' caption='[[2poa]], [[NMR_Ensembles_of_Models | 17 NMR models]]' scene=''> | <StructureSection load='2poa' size='340' side='right' caption='[[2poa]], [[NMR_Ensembles_of_Models | 17 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2poa]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2poa]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/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'>[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> | </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=2poa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2poa OCA], [http://pdbe.org/2poa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2poa RCSB], [http://www.ebi.ac.uk/pdbsum/2poa PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| Line 25: | Line 25: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2poa" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
| Line 32: | Line 33: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Blood fluke]] | ||
[[Category: Ho, P L]] | [[Category: Ho, P L]] | ||
[[Category: Oyama, S]] | [[Category: Oyama, S]] | ||
| Line 43: | Line 44: | ||
[[Category: Molecular dynamic]] | [[Category: Molecular dynamic]] | ||
[[Category: Protein stability]] | [[Category: Protein stability]] | ||
[[Category: Schistosoma mansoni]] | |||
[[Category: Site directed mutagenesis]] | [[Category: Site directed mutagenesis]] | ||
[[Category: Vaccine antigen]] | [[Category: Vaccine antigen]] | ||
Revision as of 13:45, 10 September 2015
Schistosoma mansoni Sm14 Fatty Acid-Binding Protein: improvement of protein stability by substitution of the single Cys62 residueSchistosoma mansoni Sm14 Fatty Acid-Binding Protein: improvement of protein stability by substitution of the single Cys62 residue
Structural highlights
Function[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 Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||