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

Effect of dimerization on dihydrofolate reductase catalysis

Guo, Jiannan, Loveridge, Edric Joel, Luk, Louis Yu Pan ORCID: and Allemann, Rudolf Konrad ORCID: 2013. Effect of dimerization on dihydrofolate reductase catalysis. Biochemistry 52 (22) , pp. 3881-3887. 10.1021/bi4005073

Full text not available from this repository.


Dihydrofolate reductase (DHFR) from the hyperthermophile Thermotoga maritima (TmDHFR) forms a very stable homodimer, while DHFRs from other organisms are monomers. We investigated the effect of dimerization on DHFR catalysis by preparing a dimeric variant, Xet-3, of DHFR from Escherichia coli (EcDHFR). Introducing residues located at the TmDHFR dimer interface into EcDHFR increases the melting temperature to 60 °C, approximately 9 °C higher than that measured for EcDHFR. The steady-state and pre-steady-state rate constants measured for Xet-3 were similar to those of dimeric TmDHFR but significantly lower than those of the parent EcDHFR. This reduction in the degree of catalytic competence is likely a consequence of the loss of flexibility of catalytically important loop regions of EcDHFR on dimerization and a compromise of the electrostatic environment of the active site. In contrast, the reduced catalytic ability of TmDHFR relative to that of EcDHFR is not simply a consequence of reduced loop flexibility in the dimeric enzyme. Our studies demonstrate that EcDHFR is not a good model for understanding the properties of other DHFRs, including TmDHFR.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Cardiff Catalysis Institute (CCI)
Subjects: Q Science > QD Chemistry
Publisher: American Chemical Society
ISSN: 0006-2960
Funders: BBSRC
Last Modified: 25 Oct 2022 09:46

Citation Data

Cited 9 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item