Structural insights into the prereaction state of pyruvate decarboxylase from Zymomonas mobilis .

Biochemistry
Xue-Yuan PeiFinian Leeper

Abstract

Pyruvate decarboxylase (PDC) uses thiamine diphosphate as an essential cofactor to catalyze the formation of acetaldehyde on the pathway of ethanol synthesis. Here we report the crystallographic image of a prereaction intermediate of a bacterial pyruvate decarboxylase prepared by cocrystallizing the enzyme with pyruvate and a stable analogue of the cofactor's activated ylid form. A second crystal structure of PDC in complex with fluoride shows that the ion organizes a water molecule that occludes the pyruvate binding site, accounting for the inhibitory effect of the halide. Also reported is a structure of the cofactor-free apo form, which when compared to the structure of the holo form indicates how thiamine diphosphate organizes the active site pocket of pyruvate decarboxylase to support catalysis. Guided by the structural and enzymatic data, we propose roles for several key residues in the catalytic mechanism.

References

May 6, 1994·Journal of Molecular Biology·M NikkolaG Schneider
Jan 3, 1997·Science·D KernG Hübner
Aug 15, 1997·European Journal of Biochemistry·G SchenkR G Duggleby
Jul 10, 1998·Biochimica Et Biophysica Acta·A Schellenberger
Jul 2, 2003·Biochemistry·Kai TittmannGerhard Hübner
Jun 10, 2004·Organic & Biomolecular Chemistry·Stéphane MannFinian J Leeper
May 9, 2006·Nature Chemical Biology·Georg WilleKai Tittmann
Oct 2, 2007·The Journal of Biological Chemistry·Wim VerséesJan Steyaert
Dec 17, 2008·Organic & Biomolecular Chemistry·Karl M ErixonFinian J Leeper

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Citations

Jun 12, 2013·Nature Chemical Biology·Danilo MeyerKai Tittmann
Apr 18, 2012·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Swati Sharma, Marc Madou
Oct 22, 2015·Chembiochem : a European Journal of Chemical Biology·Cindy WechslerKai Tittmann
Jan 17, 2012·Bioorganic Chemistry·Forest H Andrews, Michael J McLeish
Nov 29, 2012·Chemical Society Reviews·Massimo Cametti, Kari Rissanen
Sep 8, 2016·Acta Crystallographica. Section F, Structural Biology Communications·Lisa BuddrusSusan J Crennell
Mar 3, 2018·Acta Crystallographica. Section F, Structural Biology Communications·Lisa BuddrusSusan J Crennell
Jul 14, 2018·Biotechnology for Biofuels·Deanne W SammondYannick J Bomble
Jun 9, 2021·The Protein Journal·Aişe ÜnlüBarış Binay
Nov 11, 2021·Journal of Agricultural and Food Chemistry·Qingxuan MuBo Yu

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Methods Mentioned

BETA
X-ray

Software Mentioned

MOSFLM
REFMAC
CNS
AMORE CCP4
PRODRG2
TRUNCATE
SCALA

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