View source for 2ofj


==Crystal structure of the E190A mutant of o-succinylbenzoate synthase from Escherichia coli==
<StructureSection load='2ofj' size='340' side='right'caption='[[2ofj]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ofj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_str._K-12_substr._MG1655 Escherichia coli str. K-12 substr. MG1655]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OFJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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=2ofj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ofj OCA], [https://pdbe.org/2ofj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ofj RCSB], [https://www.ebi.ac.uk/pdbsum/2ofj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ofj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MENC_ECOLI MENC_ECOLI] Converts SHCHC to OSB.
== 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/of/2ofj_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=2ofj ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Enzyme catalysis reflects a dynamic interplay between charged and polar active site residues that facilitate function, stabilize transition states, and maintain overall protein stability. Previous studies show that substituting neutral for charged residues in the active site often significantly stabilizes a protein, suggesting a stability trade-off for functionality. In the enolase superfamily, a set of conserved active site residues (the "catalytic module") has repeatedly been used in nature in the evolution of many different enzymes for the performance of unique overall reactions involving a chemically diverse set of substrates. This catalytic module provides a robust solution for catalysis that delivers the common underlying partial reaction that supports all of the different overall chemical reactions of the superfamily. As this module has been so broadly conserved in the evolution of new functions, we sought to investigate the extent to which it follows the stability-function trade-off. Alanine substitutions were made for individual residues, groups of residues, and the entire catalytic module of o-succinylbenzoate synthase (OSBS), a member of the enolase superfamily from Escherichia coli. Of six individual residue substitutions, four (K131A, D161A, E190A, and D213A) substantially increased protein stability (by 0.46-4.23 kcal/mol), broadly consistent with prediction of a stability-activity trade-off. The residue most conserved across the superfamily, E190, is by far the most destabilizing. When the individual substitutions were combined into groups (as they are structurally and functionally organized), nonadditive stability effects emerged, supporting previous observations that residues within the module interact as two functional groups within a larger catalytic system. Thus, whereas the multiple-mutant enzymes D161A/E190A/D213A and K131A/K133A/D161A/E190A/D213A/K235A (termed 3KDED) are stabilized relative to the wild-type enzyme (by 1.77 and 3.68 kcal/mol, respectively), the net stabilization achieved in both cases is much weaker than what would be predicted if their stability contributions were additive. Organization of the catalytic module into systems that mitigate the expected stability cost due to the presence of highly charged active site residues may help to explain its repeated use for the evolution of many different functions.

Stability for function trade-offs in the enolase superfamily "catalytic module".,Nagatani RA, Gonzalez A, Shoichet BK, Brinen LS, Babbitt PC Biochemistry. 2007 Jun 12;46(23):6688-95. Epub 2007 May 16. PMID:17503785<ref>PMID:17503785</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2ofj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli str. K-12 substr. MG1655]]
[[Category: Large Structures]]
[[Category: Babbitt PC]]
[[Category: Brinen LS]]
[[Category: Gonzalez A]]
[[Category: Nagatani RA]]
[[Category: Shoichet BK]]