Loop Interactions during Catalysis by Dihydrofolate Reductase from Moritella profunda

Behiry, Enas Mamdouh, Evans, Rhiannon Mari, Guo, Jian Nan, Loveridge, Edric Joel and Allemann, Rudolf Konrad ORCID: https://orcid.org/0000-0002-1323-8830 2014. Loop Interactions during Catalysis by Dihydrofolate Reductase from Moritella profunda. Biochemistry 53 (29) , pp. 4769-4774. 10.1021/bi500508z

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Abstract

Dihydrofolate reductase (DHFR) is often used as a model system to study the relation between protein dynamics and catalysis. We have studied a number of variants of the cold-adapted DHFR from Moritella profunda (MpDHFR), in which the catalytically important M20 and FG loops have been altered, and present a comparison with the corresponding variants of the wellstudied DHFR from Escherichia coli (EcDHFR). Mutations in the M20 loop do not affect the actual chemical step of transfer of hydride from reduced nicotinamide adenine dinucleotide phosphate to the substrate 7,8-dihydrofolate in the catalytic cycle in either enzyme; they affect the steady state turnover rate in EcDHFR but not in MpDHFR. Mutations in the FG loop also have different effects on catalysis by the two DHFRs. Despite the two enzymes most likely sharing a common catalytic cycle at pH 7, motions of these loops, known to be important for progression through the catalytic cycle in EcDHFR, appear not to play a significant role in MpDHFR.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Chemistry
Subjects:	Q Science > QD Chemistry
Publisher:	ACS Publications
ISSN:	0006-2960
Funders:	BBSRC
Date of First Compliant Deposit:	30 March 2016
Last Modified:	23 May 2023 16:01
URI:	https://orca.cardiff.ac.uk/id/eprint/63605

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