The hydrolysis of 6-phosphogluconolactone in the second step of pentose phosphate pathway occurs via a two-water mechanism

Autoren

Tabeer Fatima
Sadaf Rani
Stefan Fischer
Thomas Efferth
Farooq Ahmad Kiani

DOI

10.1016/j.bpc.2018.06.002

ISSN

0301-4622

Zeitschrift

Biophysical Chemistry

Sprache

en

Paginierung

98 - 106

Datum der Veröffentlichung

2018

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.bpc.2018.06.002

Datum der Datenerfassung

2022

Titel

The hydrolysis of 6-phosphogluconolactone in the second step of pentose phosphate pathway occurs via a two-water mechanism

Ausgabe der Zeitschrift

240

Data source: Crossref

Abstract

Hydrolysis reaction marks the basis of life yet the mechanism of this crucial biochemical reaction is not completely understood. We recently reported the mechanisms of hydrolysis of nucleoside triphosphate and phosphate monoester. These two reactions hydrolyze P-O-P and P-O-C linkages, respectively. Here, we present the mechanism of hydrolysis of δ-6-phosphogluconolactone, which is an important precursor in the second step of the pentose phosphate pathway. Its hydrolysis requires the cleavage of C-O-C linkage and its mechanism is hitherto unknown. We report three mechanisms of hydrolysis of δ-6-phosphogluconolactone based on density functional computations. In the energetically most favorable mechanism, two water molecules participate in the hydrolysis reaction and the mechanism is sequential, i.e., activation of the attacking water molecule (OH bond breaking) precedes that of the cleavage of the CO bond of the C-O-C linkage. The rate-limiting energy barrier of this mechanism is comparable to the reported experimental free energy barrier. This mechanism has similarities with the mechanism of triphosphate hydrolysis and that of hydrolytic cleavage of DNA in EcoRV enzyme. This two-water sequential hydrolysis mechanism could be the unified mechanism required for the hydrolysis of other hydrolysable species in living cells.

Addresses

Research Center for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), Sector H-12, 44000 Islamabad, Pakistan; Department of Biotechnology, University of Sialkot, 51310 Sialkot, Pakistan.

Autoren

Tabeer Fatima
Sadaf Rani
Stefan Fischer
Thomas Efferth
Farooq Ahmad Kiani

DOI

10.1016/j.bpc.2018.06.002

eISSN

1873-4200

Externe Identifier

PubMed Identifier: 30014892

Open access

false

ISSN

0301-4622

Zeitschrift

Biophysical chemistry

Schlüsselwörter

Water
Gluconates
Binding Sites
Hydrolysis
Quantum Theory
Thermodynamics
Models, Molecular
Pentose Phosphate Pathway

Sprache

eng

Medium

Print-Electronic

Online publication date

2018

Paginierung

98 - 106

Datum der Veröffentlichung

2018

Status

Published

Datum der Datenerfassung

2018

Titel

The hydrolysis of 6-phosphogluconolactone in the second step of pentose phosphate pathway occurs via a two-water mechanism.

Sub types

Journal Article

Ausgabe der Zeitschrift

240

Data source: Europe PubMed Central

Abstract

Hydrolysis reaction marks the basis of life yet the mechanism of this crucial biochemical reaction is not completely understood. We recently reported the mechanisms of hydrolysis of nucleoside triphosphate and phosphate monoester. These two reactions hydrolyze P-O-P and P-O-C linkages, respectively. Here, we present the mechanism of hydrolysis of δ-6-phosphogluconolactone, which is an important precursor in the second step of the pentose phosphate pathway. Its hydrolysis requires the cleavage of C-O-C linkage and its mechanism is hitherto unknown. We report three mechanisms of hydrolysis of δ-6-phosphogluconolactone based on density functional computations. In the energetically most favorable mechanism, two water molecules participate in the hydrolysis reaction and the mechanism is sequential, i.e., activation of the attacking water molecule (OH bond breaking) precedes that of the cleavage of the CO bond of the C-O-C linkage. The rate-limiting energy barrier of this mechanism is comparable to the reported experimental free energy barrier. This mechanism has similarities with the mechanism of triphosphate hydrolysis and that of hydrolytic cleavage of DNA in EcoRV enzyme. This two-water sequential hydrolysis mechanism could be the unified mechanism required for the hydrolysis of other hydrolysable species in living cells.

Date of acceptance

2018

Autoren

Tabeer Fatima
Sadaf Rani
Stefan Fischer
Thomas Efferth
Farooq Ahmad Kiani

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/30014892

DOI

10.1016/j.bpc.2018.06.002

eISSN

1873-4200

Zeitschrift

Biophys Chem

Schlüsselwörter

6-Phosphogluconolactonase enzyme
Catalytic mechanism
Computational biochemistry
Hydrolysis reaction
Pentose phosphate pathway
Binding Sites
Gluconates
Hydrolysis
Models, Molecular
Pentose Phosphate Pathway
Quantum Theory
Thermodynamics
Water

Sprache

eng

Country

Netherlands

Paginierung

98 - 106

PII

S0301-4622(18)30135-2

Datum der Veröffentlichung

2018

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2018

Titel

The hydrolysis of 6-phosphogluconolactone in the second step of pentose phosphate pathway occurs via a two-water mechanism.

Sub types

Journal Article

Ausgabe der Zeitschrift

240

Data source: PubMed

The hydrolysis of 6-phosphogluconolactone in the second step of pentose phosphate pathway occurs via a two-water mechanism

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