Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Protein motions during catalysis by dihydrofolate reductases

Allemann, Rudolf Konrad, Evans, Rhiannon Mari, Tey, Lai-Hock, Maglia, G., Pang, Jiayun, Rodriguez, Robert, Shrimpton, P. J. and Swanwick, Richard S. 2006. Protein motions during catalysis by dihydrofolate reductases. Philosophical Transactions of the Royal Society of London Series B - Biological Sciences 361 (1472) , pp. 1317-1321. 10.1098/rstb.2006.1865

Full text not available from this repository.

Abstract

Dihydrofolate reductase (DHFR) maintains the intracellular pool of tetrahydrofolate through catalysis of hydrogen transfer from reduced nicotinamide adenine dinucleotide to 7,8-dihydrofolate. We report results for pre-steady-state kinetic studies of the temperature dependence of the rates and the hydrogen/deuterium-kinetic isotope effects for the reactions catalysed by the enzymes from the mesophilic Escherichia coli and the hyperthermophilic Thermatoga maritima. We propose an evolutionary pattern in which catalysis progressed from a relatively rigid active site structure in the ancient thermophilic DHFR to a more flexible and kinetically more efficient structure in E. coli that actively promotes hydrogen transfer at physiological pH by modulating the tunnelling distance. The E. coli enzyme appeared relatively robust, in that kinetically severely compromised mutants still actively propagated the reaction. The reduced hydrogen transfer rates of the extensively studied Gly121Val mutant of DHFR from E. coli were most likely due to sterically unfavourable long-range effects from the introduction of the bulky isopropyl group.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Cardiff Catalysis Institute (CCI)
Subjects: Q Science > QD Chemistry
Uncontrolled Keywords: hydrogen transfer; kinetic isotope effects; protein dynamics; catalysis; enzymes
Publisher: Royal Society
ISSN: 0962-8436
Last Modified: 04 Feb 2018 01:25
URI: http://orca.cf.ac.uk/id/eprint/13242

Citation Data

Cited 25 times in Google Scholar. View in Google Scholar

Cited 22 times in Scopus. View in Scopus. Powered By Scopus® Data

Cited 18 times in Web of Science. View in Web of Science.

Actions (repository staff only)

Edit Item Edit Item