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Small-molecules that covalently react with a human prolyl hydroxylase - towards activity modulation and substrate capture.

ABSTRACT: We describe covalently binding modulators of the activity of human prolyl hydroxylase domain 2 (PHD2) and studies towards a strategy for photocapture of PHD2 substrates. Reversible active site binding of electrophile bearing compounds enables susbsequent covalent reaction with a lysine residue (K408) in the flexible C-terminal region of PHD2 to give a modified protein that retains catalytic activity.

SUBMITTER: Bush JT

PROVIDER: S-EPMC6350621 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Small-molecules that covalently react with a human prolyl hydroxylase - towards activity modulation and substrate capture.

Bush Jacob T JT Leśniak Robert K RK Yeh Tzu-Lan TL Belle Roman R Kramer Holger H Tumber Anthony A Chowdhury Rasheduzzaman R Flashman Emily E Mecinović Jasmin J Schofield Christopher J CJ

Chemical communications (Cambridge, England) 20190101 8

We describe covalently binding modulators of the activity of human prolyl hydroxylase domain 2 (PHD2) and studies towards a strategy for photocapture of PHD2 substrates. Reversible active site binding of electrophile bearing compounds enables susbsequent covalent reaction with a lysine residue (K408) in the flexible C-terminal region of PHD2 to give a modified protein that retains catalytic activity. ...[more]

PMID: 30452037

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