3csm: Difference between revisions
New page: left|200px<br /> <applet load="3csm" size="450" color="white" frame="true" align="right" spinBox="true" caption="3csm, resolution 3.0Å" /> '''STRUCTURE OF YEAST C... |
No edit summary |
||
| (19 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==STRUCTURE OF YEAST CHORISMATE MUTASE WITH BOUND TRP AND AN ENDOOXABICYCLIC INHIBITOR== | ||
BACKGROUND: Chorismate mutase (CM) catalyzes the Claisen rearrangement of | <StructureSection load='3csm' size='340' side='right'caption='[[3csm]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3csm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CSM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CSM 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]] 3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene>, <scene name='pdbligand=TSA:8-HYDROXY-2-OXA-BICYCLO[3.3.1]NON-6-ENE-3,5-DICARBOXYLIC+ACID'>TSA</scene></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=3csm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3csm OCA], [https://pdbe.org/3csm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3csm RCSB], [https://www.ebi.ac.uk/pdbsum/3csm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3csm ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CHMU_YEAST CHMU_YEAST] | |||
== 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/cs/3csm_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=3csm ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
BACKGROUND: Chorismate mutase (CM) catalyzes the Claisen rearrangement of chorismate to prephenate, notably the only known enzymatically catalyzed pericyclic reaction in primary metabolism. Structures of the enzyme in complex with an endo-oxabicyclic transition state analogue inhibitor, previously determined for Bacillus subtilis and Escherichia coli CM, provide structural insight into the enzyme mechanism. In contrast to these bacterial CMs, yeast CM is allosterically regulated in two ways: activation by tryptophan and inhibition by tyrosine. Yeast CM exists in two allosteric states, R (active) and t (inactive). RESULTS: We have determined crystal structures of wild-type yeast CM cocrystallized with tryptophan and an endo-oxabicyclic transition state analogue inhibitor, of wild-type yeast CM co-crystallized with tyrosine and the endo-oxabicyclic transition state analogue inhibitor and of the Thr226-->Ser mutant of yeast CM in complex with tryptophan. Binding of the transition state analogue inhibitor to CM keeps the enzyme in a 'super R' state, even if the inhibitory effector tyrosine is bound to the regulatory site. CONCLUSIONS: The endo-oxabicyclic inhibitor binds to yeast CM in a similar way as it does to the distantly related CM from E. coli. The inhibitor-binding mode supports a mechanism by which polar sidechains of the enzyme bind the substrate in the pseudo-diaxial conformation, which is required for catalytic turnover. A lysine and a protonated glutamate sidechain have a critical role in the stabilization of the transition state of the pericyclic reaction. The allosteric transition from T-->R state is accompanied by a 15 degrees rotation of one of the two subunits relative to the other (where 0 degrees rotation defines the T state). This rotation causes conformational changes at the dimer interface which are transmitted to the active site. An allosteric pathway is proposed to include residues Phe28, Asp24 and Glu23, which move toward the activesite cavity in the T state. In the presence of the transition-state analogue a super R state is formed, which is characterised by a 22 degrees rotation of one subunit relative to the other. | |||
Mechanisms of catalysis and allosteric regulation of yeast chorismate mutase from crystal structures.,Strater N, Schnappauf G, Braus G, Lipscomb WN Structure. 1997 Nov 15;5(11):1437-52. PMID:9384560<ref>PMID:9384560</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
<div class="pdbe-citations 3csm" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[3D structures of chorismate mutase|3D structures of chorismate mutase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Braus G]] | |||
[[Category: Braus | [[Category: Lipscomb WN]] | ||
[[Category: Lipscomb | [[Category: Schnappauf G]] | ||
[[Category: Schnappauf | [[Category: Straeter N]] | ||
[[Category: Straeter | |||
Latest revision as of 09:47, 9 August 2023
STRUCTURE OF YEAST CHORISMATE MUTASE WITH BOUND TRP AND AN ENDOOXABICYCLIC INHIBITORSTRUCTURE OF YEAST CHORISMATE MUTASE WITH BOUND TRP AND AN ENDOOXABICYCLIC INHIBITOR
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBACKGROUND: Chorismate mutase (CM) catalyzes the Claisen rearrangement of chorismate to prephenate, notably the only known enzymatically catalyzed pericyclic reaction in primary metabolism. Structures of the enzyme in complex with an endo-oxabicyclic transition state analogue inhibitor, previously determined for Bacillus subtilis and Escherichia coli CM, provide structural insight into the enzyme mechanism. In contrast to these bacterial CMs, yeast CM is allosterically regulated in two ways: activation by tryptophan and inhibition by tyrosine. Yeast CM exists in two allosteric states, R (active) and t (inactive). RESULTS: We have determined crystal structures of wild-type yeast CM cocrystallized with tryptophan and an endo-oxabicyclic transition state analogue inhibitor, of wild-type yeast CM co-crystallized with tyrosine and the endo-oxabicyclic transition state analogue inhibitor and of the Thr226-->Ser mutant of yeast CM in complex with tryptophan. Binding of the transition state analogue inhibitor to CM keeps the enzyme in a 'super R' state, even if the inhibitory effector tyrosine is bound to the regulatory site. CONCLUSIONS: The endo-oxabicyclic inhibitor binds to yeast CM in a similar way as it does to the distantly related CM from E. coli. The inhibitor-binding mode supports a mechanism by which polar sidechains of the enzyme bind the substrate in the pseudo-diaxial conformation, which is required for catalytic turnover. A lysine and a protonated glutamate sidechain have a critical role in the stabilization of the transition state of the pericyclic reaction. The allosteric transition from T-->R state is accompanied by a 15 degrees rotation of one of the two subunits relative to the other (where 0 degrees rotation defines the T state). This rotation causes conformational changes at the dimer interface which are transmitted to the active site. An allosteric pathway is proposed to include residues Phe28, Asp24 and Glu23, which move toward the activesite cavity in the T state. In the presence of the transition-state analogue a super R state is formed, which is characterised by a 22 degrees rotation of one subunit relative to the other. Mechanisms of catalysis and allosteric regulation of yeast chorismate mutase from crystal structures.,Strater N, Schnappauf G, Braus G, Lipscomb WN Structure. 1997 Nov 15;5(11):1437-52. PMID:9384560[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
| ||||||||||||||||||