Application of a Proteolysis/Mass Spectrometry Method for Investigating the Effects of Inhibitors on Hydroxylase Structure

被引：41
作者：
Stubbs, Christopher J. [1 ,2 ]
Loenarz, Christoph [1 ,2 ]
Mecinovic, Jasmin [1 ,2 ]
Yeoh, Kar Kheng [1 ,2 ]
Hindley, Nicola [1 ,2 ]
Lienard, Benoit M. [1 ,2 ]
Sobott, Frank
Schofield, Christopher J. [1 ,2 ]
Flashman, Emily [1 ,2 ]
机构：
[1] Univ Oxford, Dept Chem, Oxford OX1 3TA, England
[2] Univ Oxford, Oxford Ctr Integrat Syst Biol, Oxford OX1 3TA, England
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 09期
基金：
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词：
HYPOXIA-INDUCIBLE FACTOR; PROLYL HYDROXYLASE; LIMITED PROTEOLYSIS; MASS-SPECTROMETRY; FACTOR HIF; CRYSTAL-STRUCTURE; BINDING-SITE; FACTOR-I; 2-OXOGLUTARATE; IDENTIFICATION;
D O I：
10.1021/jm900285r
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Limited proteolysis coupled to matrix-assisted laser desorption/ionization (MALDI) mass spectrometric analyses can be used to screen for compounds that alter protein structure by monitoring stabilizing/destabilizing effects with respect to the rate and nature of proteolysis. When applied to prolyl hydroxylase 2, a hey enzyme involved in human oxygen sensing. the method efficiently revealed differential effects on proteolytic stability for structurally similar compounds and for different substrates.
引用
收藏
页码：2799 / 2805
页数：7
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