3csm: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:3csm.gif|left|200px]] | [[Image:3csm.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_3csm", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
| | or leave the SCENE parameter empty for the default display. | ||
| | --> | ||
{{STRUCTURE_3csm| PDB=3csm | SCENE= }} | |||
}} | |||
'''STRUCTURE OF YEAST CHORISMATE MUTASE WITH BOUND TRP AND AN ENDOOXABICYCLIC INHIBITOR''' | '''STRUCTURE OF YEAST CHORISMATE MUTASE WITH BOUND TRP AND AN ENDOOXABICYCLIC INHIBITOR''' | ||
| Line 30: | Line 27: | ||
[[Category: Schnappauf, G.]] | [[Category: Schnappauf, G.]] | ||
[[Category: Straeter, N.]] | [[Category: Straeter, N.]] | ||
[[Category: | [[Category: Allosteric protein]] | ||
[[Category: | [[Category: Chorismate pyruvatemutase]] | ||
[[Category: | [[Category: Transition state analog]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 21:58:37 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 21:58, 4 May 2008
STRUCTURE OF YEAST CHORISMATE MUTASE WITH BOUND TRP AND AN ENDOOXABICYCLIC INHIBITOR
OverviewOverview
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.
About this StructureAbout this Structure
3CSM is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
ReferenceReference
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 Page seeded by OCA on Sun May 4 21:58:37 2008