Temporally overlapped but uncoupled motions in dihydrofolate reductase catalysis

C. Tony Liu, Lin Wang, Nina Goodey, Philip Hanoian, Stephen J. Benkovic

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

Temporal correlations between protein motions and enzymatic reactions are often interpreted as evidence for catalytically important motions. Using dihydrofolate reductase as a model system, we show that there are many protein motions that temporally overlapped with the chemical reaction, and yet they do not exhibit the same kinetic behaviors (KIE and pH dependence) as the catalyzed chemical reaction. Thus, despite the temporal correlation, these motions are not directly coupled to the chemical transformation, and they might represent a different part of the catalytic cycle or simply be the product of the intrinsic flexibility of the protein.

Original languageEnglish
Pages (from-to)5332-5334
Number of pages3
JournalBiochemistry
Volume52
Issue number32
DOIs
StatePublished - 13 Aug 2013

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Tetrahydrofolate Dehydrogenase
Catalysis
Chemical reactions
Proteins
Kinetics

Cite this

Liu, C. Tony ; Wang, Lin ; Goodey, Nina ; Hanoian, Philip ; Benkovic, Stephen J. / Temporally overlapped but uncoupled motions in dihydrofolate reductase catalysis. In: Biochemistry. 2013 ; Vol. 52, No. 32. pp. 5332-5334.
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Temporally overlapped but uncoupled motions in dihydrofolate reductase catalysis. / Liu, C. Tony; Wang, Lin; Goodey, Nina; Hanoian, Philip; Benkovic, Stephen J.

In: Biochemistry, Vol. 52, No. 32, 13.08.2013, p. 5332-5334.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Temporally overlapped but uncoupled motions in dihydrofolate reductase catalysis

AU - Liu, C. Tony

AU - Wang, Lin

AU - Goodey, Nina

AU - Hanoian, Philip

AU - Benkovic, Stephen J.

PY - 2013/8/13

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N2 - Temporal correlations between protein motions and enzymatic reactions are often interpreted as evidence for catalytically important motions. Using dihydrofolate reductase as a model system, we show that there are many protein motions that temporally overlapped with the chemical reaction, and yet they do not exhibit the same kinetic behaviors (KIE and pH dependence) as the catalyzed chemical reaction. Thus, despite the temporal correlation, these motions are not directly coupled to the chemical transformation, and they might represent a different part of the catalytic cycle or simply be the product of the intrinsic flexibility of the protein.

AB - Temporal correlations between protein motions and enzymatic reactions are often interpreted as evidence for catalytically important motions. Using dihydrofolate reductase as a model system, we show that there are many protein motions that temporally overlapped with the chemical reaction, and yet they do not exhibit the same kinetic behaviors (KIE and pH dependence) as the catalyzed chemical reaction. Thus, despite the temporal correlation, these motions are not directly coupled to the chemical transformation, and they might represent a different part of the catalytic cycle or simply be the product of the intrinsic flexibility of the protein.

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