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Title: Structure of Arabidopsis Dehydroquinate Dhydratase-Shikimate Dehydrogeanse and Implications for Metabolic Channeling in the Shikimate Pathway

Abstract

The bifunctional enzyme dehydroquinate dehydratase-shikimate dehydrogenase (DHQ-SDH) catalyzes the dehydration of dehydroquinate to dehydroshikimate and the reduction of dehydroshikimate to shikimate in the shikimate pathway. We report the first crystal structure of Arabidopsis DHQ-SDH with shikimate bound at the SDH site and tartrate at the DHQ site. The interactions observed in the DHQ-tartrate complex reveal a conserved mode for substrate binding between the plant and microbial DHQ dehydratase family of enzymes. The SDH-shikimate complex provides the first direct evidence of the role of active site residues in the catalytic mechanism. Site-directed mutagenesis and mechanistic analysis revealed that Asp 423 and Lys 385 are key catalytic groups and Ser 336 is a key binding group. The arrangement of the two functional domains reveals that the control of metabolic flux through the shikimate pathway is achieved by increasing the effective concentration of dehydroshikimate through the proximity of the two sites.

Authors:
;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
914078
Report Number(s):
BNL-78646-2007-JA
Journal ID: ISSN 0006-2960; BICHAW; TRN: US0801525
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemistry; Journal Volume: 45
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; 43 PARTICLE ACCELERATORS; ARABIDOPSIS; CHANNELING; CRYSTAL STRUCTURE; DEHYDRATION; ENZYMES; FUNCTIONALS; MUTAGENESIS; RESIDUES; SUBSTRATES; TARTRATES; NSLS; national synchrotron light source

Citation Formats

Singh,S., and Christendat, D. Structure of Arabidopsis Dehydroquinate Dhydratase-Shikimate Dehydrogeanse and Implications for Metabolic Channeling in the Shikimate Pathway. United States: N. p., 2006. Web. doi:10.1021/bi060366+.
Singh,S., & Christendat, D. Structure of Arabidopsis Dehydroquinate Dhydratase-Shikimate Dehydrogeanse and Implications for Metabolic Channeling in the Shikimate Pathway. United States. doi:10.1021/bi060366+.
Singh,S., and Christendat, D. Sun . "Structure of Arabidopsis Dehydroquinate Dhydratase-Shikimate Dehydrogeanse and Implications for Metabolic Channeling in the Shikimate Pathway". United States. doi:10.1021/bi060366+.
@article{osti_914078,
title = {Structure of Arabidopsis Dehydroquinate Dhydratase-Shikimate Dehydrogeanse and Implications for Metabolic Channeling in the Shikimate Pathway},
author = {Singh,S. and Christendat, D.},
abstractNote = {The bifunctional enzyme dehydroquinate dehydratase-shikimate dehydrogenase (DHQ-SDH) catalyzes the dehydration of dehydroquinate to dehydroshikimate and the reduction of dehydroshikimate to shikimate in the shikimate pathway. We report the first crystal structure of Arabidopsis DHQ-SDH with shikimate bound at the SDH site and tartrate at the DHQ site. The interactions observed in the DHQ-tartrate complex reveal a conserved mode for substrate binding between the plant and microbial DHQ dehydratase family of enzymes. The SDH-shikimate complex provides the first direct evidence of the role of active site residues in the catalytic mechanism. Site-directed mutagenesis and mechanistic analysis revealed that Asp 423 and Lys 385 are key catalytic groups and Ser 336 is a key binding group. The arrangement of the two functional domains reveals that the control of metabolic flux through the shikimate pathway is achieved by increasing the effective concentration of dehydroshikimate through the proximity of the two sites.},
doi = {10.1021/bi060366+},
journal = {Biochemistry},
number = ,
volume = 45,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}