Thermal Adaptation of Dihydrofolate Reductase from the Moderate Thermophile Geobacillus Stearothermophilus

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2014 Apr 16

PMID 24730604

Citations 4

Authors

Jiannan Guo

Louis Y P Luk

E Joel Loveridge

Rudolf K Allemann

Affiliations

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Abstract

The thermal melting temperature of dihydrofolate reductase from Geobacillus stearothermophilus (BsDHFR) is ~30 °C higher than that of its homologue from the psychrophile Moritella profunda. Additional proline residues in the loop regions of BsDHFR have been proposed to enhance the thermostability of BsDHFR, but site-directed mutagenesis studies reveal that these proline residues contribute only minimally. Instead, the high thermal stability of BsDHFR is partly due to removal of water-accessible thermolabile residues such as glutamine and methionine, which are prone to hydrolysis or oxidation at high temperatures. The extra thermostability of BsDHFR can be obtained by ligand binding, or in the presence of salts or cosolvents such as glycerol and sucrose. The sum of all these incremental factors allows BsDHFR to function efficiently in the natural habitat of G. stearothermophilus, which is characterized by temperatures that can reach 75 °C.

Citing Articles

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Adesina A, Luk L, Allemann R Chembiochem. 2021; 22(14):2410-2414.

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A Method for Prediction of Thermophilic Protein Based on Reduced Amino Acids and Mixed Features.

Feng C, Ma Z, Yang D, Li X, Zhang J, Li Y Front Bioeng Biotechnol. 2020; 8:285.

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Minimization of dynamic effects in the evolution of dihydrofolate reductase.

Ruiz-Pernia J, Behiry E, Luk L, Loveridge E, Tunon I, Moliner V Chem Sci. 2018; 7(5):3248-3255.

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Halophilic mechanism of the enzymatic function of a moderately halophilic dihydrofolate reductase from Haloarcula japonica strain TR-1.

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