Binding Isotope Effects for Interrogating Enzyme-Substrate Interactions

被引：4

作者：

Stratton, Christopher F. ^{[1
,2
]}

Poulin, Myles B. ^{[1
,3
]}

Schramm, Vern L. ^{[1
]}

机构：

[1] Albert Einstein Coll Med, Bronx, NY 10467 USA

[2] Pfizer Inc, Groton, CT 06340 USA

[3] Univ Maryland, College Pk, MD 20742 USA

来源：

MEASUREMENT AND ANALYSIS OF KINETIC ISOTOPE EFFECTS | 2017年 / 596卷

关键词：

TRANSITION-STATE; BONDING ENVIRONMENT; METHYLTRANSFERASE; DESTABILIZATION; GLUCOSE; COMPLEX;

D O I：

10.1016/bs.mie.2017.07.019

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Equilibrium binding isotope effects (BIEs) report on the bond vibrational status of enzyme substrates in the Michaelis complex prior to the transition state and how they differ from the solution state. Accordingly, BIEs provide an experimental means of interrogating enzyme-substrate interactions and inform on the influence of enzymemediated atomic distortions in modulating substrate reactivity. In this chapter, we outline a rapid equilibrium dialysis method that our lab has used to measure BIEs for several enzyme systems. Implementation of the rapid equilibrium dialysis approach is described in the context of our recent studies on the substrate bonding environment for the human protein lysine N-methyltransferase NSD2. A summary of BIE effects provides context for the range of experimental values.

引用

页码：1 / 21

页数：21

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