DOI: 10.5061/dryad.3j9kd51wz
title: The reaction mechanism for glycolysis side product degradation by Parkinson's disease-linked DJ-1

description: DJ-1/PARK7 is the causative gene for hereditary recessive Parkinson's
 disease. Recent studies have reported that DJ-1 hydrolyzes cyclic
 3-phosphoglyceric anhydride (cPGA), a highly reactive metabolite. However,
 the molecular mechanisms underlying cPGA hydrolase activity have yet to be
 fully elucidated. To gain a more comprehensive understanding of this
 activity in DJ-1, we performed molecular simulations that predicted how
 DJ-1 recognizes and hydrolyzes cPGA. The accuracy of these structural
 predictions was validated through systematic mutational analyses
 exemplified by loss of activity with the A107P mutation. Although DJ-1
 possesses both cPGA hydrolase and α-oxoaldehyde hydratase activities in
 vitro, we confirmed that DJ-1 dysfunction caused an increase in
 cPGA-derived modifications but had no effect on α-oxoaldehyde-derived
 modifications in cells. Importantly, A107 and P158, pathogenic missense
 mutation sites found in Parkinson's disease patients, are critical
 for cPGA-hydrolysis both in vitro and in cells. The evidence-based
 catalytic mechanism for DJ-1 hydrolysis of cPGA that we propose here
 explains their pathophysiological significance.
description: # The reaction mechanism for glycolysis side product degradation by
 Parkinson's disease-linked DJ-1 Dataset DOI:
 [10.5061/dryad.3j9kd51wz](10.5061/dryad.3j9kd51wz) ## Description of the
 data and file structure Absorbance data to monitor cPGA and structure
 model predicted in silico. ### Files and variables #### File:
 cPGA\_source\_data\_Figure\_1.xlsx **Description:** Source_data
 (Absorbance data) for Fig. 1 indicating the cPGA hydrolase activities of
 DJ-1 (WT or C106S mutant), YajL (WT or C106S mutant), YhbO, ElbB, and
 HchA. The data represent absorbance at 235 nm, calculated as Abs = -log₁₀T
 (T = transmittance at 235 nm). Since absorbance is a dimensionless
 quantity, no unit is assigned. #### File:
 cPGA\_source\_data\_Figure\_4.xlsx **Description:** Source_data
 (Absorbance data) for Fig. 4 indicating the cPGA hydrolase activities of
 DJ-1 mutants (WT, E15A, E18A, E18Q, R28A, or R48A) and YajL mutants (WT,
 E14A, E17A, R27A, or R49A). The data represent absorbance at 235 nm,
 calculated as Abs = -log₁₀T (T = transmittance at 235 nm). Since
 absorbance is a dimensionless quantity, no unit is assigned. #### File:
 cPGA\_source\_data\_Figure\_5.xlsx **Description:** Source_data
 (Absorbance data) for Fig. 5 indicating the cPGA hydrolase activities of
 DJ-1 mutants (WT, G74S, G75S, C106S, A107H, A107I, or A107P) and YajL
 mutants (WT, G74S, G75S, C106S, or A107P). The data represent absorbance
 at 235 nm, calculated as Abs = -log₁₀T (T = transmittance at 235 nm).
 Since absorbance is a dimensionless quantity, no unit is assigned. ####
 File: cPGA\_source\_data\_Figure\_6.xlsx **Description:** Source_data
 (Absorbance data) for Fig. 6 indicating the cPGA hydrolase activities of
 DJ-1 mutants (WT, N76W, H126A, P158A, or P158delta) and YajL mutants (WT,
 P158A, or P158delta). The data represent absorbance at 235 nm, calculated
 as Abs = -log₁₀T (T = transmittance at 235 nm). Since absorbance is a
 dimensionless quantity, no unit is assigned. #### File:
 cPGA\_source\_data\_Figure\_S3.xlsx **Description:** Source_data
 (Absorbance data) for Fig. S3 indicating the methylglyoxalase and cPGA
 hydrolase activities of DJ-1. The data represent absorbance at 288 nm and
 235 nm, calculated as Abs = -log₁₀T (T = transmittance at 288 nm or 235
 nm). Since absorbance is a dimensionless quantity, no unit is assigned.
 #### File: Fig2.pse **Description:** Structure model showing how cPGA
 interacts with DJ-1 or YajL, as predicted in silico (Fig. 2), provided as
 a PyMOL session file. Since this PyMOL session file is dimensionless, no
 unit is assigned. #### File: Fig3.pse **Description:** Structure model
 showing how dimeric structures of ElbB, HchA, and YhbO weaken cPGA
 binding, as predicted in silico (Fig. 3), provided as a PyMOL session
 file. Since this PyMOL session file is dimensionless, no unit is assigned.
 #### File: Fig5A.pse **Description:** Structure model showing how cPGA is
 recognized by G74, G75, C106, and A107 of DJ-1, as predicted in silico
 (Fig. 5), provided as a PyMOL session file. Since this PyMOL session file
 is dimensionless, no unit is assigned. #### File: Fig6A.pse
 **Description:** Structure model showing how cPGA is recognized by E18,
 R28, and P158 of DJ-1, as predicted in silico (Fig. 6), provided as a
 PyMOL session file. Since this PyMOL session file is dimensionless, no
 unit is assigned. ## Access information Other publicly accessible
 locations of the data: * Not applicable Data was derived from the
 following sources: * Not applicable