View source for 2clm

==TRYPTOPHAN SYNTHASE (EXTERNAL ALDIMINE STATE) IN COMPLEX WITH N-(4'-TRIFLUOROMETHOXYBENZOYL)-2-AMINO-1-ETHYLPHOSPHATE (F6F)==
<StructureSection load='2clm' size='340' side='right' caption='[[2clm]], [[Resolution|resolution]] 1.51&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2clm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CLM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F6F:2-{[4-(TRIFLUOROMETHOXY)BENZOYL]AMINO}ETHYL+DIHYDROGEN+PHOSPHATE'>F6F</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PLS:[3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YLMETHYL]-SERINE'>PLS</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a50|1a50]], [[1a5a|1a5a]], [[1a5b|1a5b]], [[1a5s|1a5s]], [[1beu|1beu]], [[1bks|1bks]], [[1c29|1c29]], [[1c8v|1c8v]], [[1c9d|1c9d]], [[1cw2|1cw2]], [[1cx9|1cx9]], [[1fuy|1fuy]], [[1k3u|1k3u]], [[1k7e|1k7e]], [[1k7f|1k7f]], [[1k7x|1k7x]], [[1k8x|1k8x]], [[1k8y|1k8y]], [[1k8z|1k8z]], [[1kfb|1kfb]], [[1kfc|1kfc]], [[1kfe|1kfe]], [[1kfj|1kfj]], [[1kfk|1kfk]], [[1qop|1qop]], [[1qoq|1qoq]], [[1tjp|1tjp]], [[1ttp|1ttp]], [[1ttq|1ttq]], [[1ubs|1ubs]], [[1wbj|1wbj]], [[2cle|2cle]], [[2clf|2clf]], [[2cli|2cli]], [[2clk|2clk]], [[2cll|2cll]], [[2clo|2clo]], [[2trs|2trs]], [[2tsy|2tsy]], [[2tys|2tys]], [[2wsy|2wsy]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tryptophan_synthase Tryptophan synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.20 4.2.1.20] </span></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=2clm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2clm OCA], [http://pdbe.org/2clm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2clm RCSB], [http://www.ebi.ac.uk/pdbsum/2clm PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/TRPA_SALTY TRPA_SALTY]] The alpha subunit is responsible for the aldol cleavage of indoleglycerol phosphate to indole and glyceraldehyde 3-phosphate. [[http://www.uniprot.org/uniprot/TRPB_SALTY TRPB_SALTY]] The beta subunit is responsible for the synthesis of L-tryptophan from indole and L-serine. 
== 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/cl/2clm_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=2clm ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
In the tryptophan synthase bienzyme complex, indole produced by substrate cleavage at the alpha-site is channeled to the beta-site via a 25 A long tunnel. Within the beta-site, indole and l-Ser react with pyridoxal 5'-phosphate in a two-stage reaction to give l-Trp. In stage I, l-Ser forms an external aldimine, E(Aex1), which converts to the alpha-aminoacrylate aldimine, E(A-A). Formation of E(A-A) at the beta-site activates the alpha-site &gt;30-fold. In stage II, indole reacts with E(A-A) to give l-Trp. The binding of alpha-site ligands (ASLs) exerts strong allosteric effects on the reaction of substrates at the beta-site: the distribution of intermediates formed in stage I is shifted in favor of E(A-A), and the binding of ASLs triggers a conformational change in the beta-site to a state with an increased affinity for l-Ser. Here, we compare the behavior of new ASLs as allosteric effectors of stage I with the behavior of the natural product, d-glyceraldehyde 3-phosphate. Rapid kinetics and kinetic isotope effects show these ASLs bind with affinities ranging from micro- to millimolar, and the rate-determining step for conversion of E(Aex1) to E(A-A) is increased by 8-10-fold. To derive a structure-based mechanism for stage I, X-ray structures of both the E(Aex1) and E(A-A) states complexed with the different ASLs were determined and compared with structures of the ASL complexes with the internal aldimine [Ngo, H., Harris, R., Kimmich, N., Casino, P., Niks, D., Blumenstein, L., Barends, T. R., Kulik, V., Weyand, M., Schlichting, I., and Dunn, M. F. (2007) Biochemistry 46, 7713-7727].

Allosteric regulation of substrate channeling in tryptophan synthase: modulation of the L-serine reaction in stage I of the beta-reaction by alpha-site ligands.,Ngo H, Kimmich N, Harris R, Niks D, Blumenstein L, Kulik V, Barends TR, Schlichting I, Dunn MF Biochemistry. 2007 Jul 3;46(26):7740-53. Epub 2007 Jun 9. PMID:17559232<ref>PMID:17559232</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Tryptophan synthase|Tryptophan synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Tryptophan synthase]]
[[Category: Barends, T R]]
[[Category: Blumenstein, L]]
[[Category: Dunn, M F]]
[[Category: Harris, R]]
[[Category: Kimmich, N]]
[[Category: Kulik, V]]
[[Category: Ngo, H]]
[[Category: Niks, D]]
[[Category: Schlichting, I]]
[[Category: Allosteric enzyme]]
[[Category: Amino-acid biosynthesis]]
[[Category: Aromatic amino acid biosynthesis]]
[[Category: Carbon-oxygen lyase]]
[[Category: Lyase]]
[[Category: Pyridoxal phosphate]]
[[Category: Tryptophan biosynthesis]]