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

被引：42

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：

英国惠康基金; 英国生物技术与生命科学研究理事会;

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

页码：2799 / 2805

页数：7

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