Azobenzene switch with a long-lived cis-state to photocontrol the enzyme activity of a histone deacetylase-like amidohydrolase
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Michael Korbus
Abstract
The control of enzymes by use of an external stimulus such as light enables the temporal and spatial regulation of defined chemical reactions in a highly precise manner. In this work we investigated and characterized the reversible photocontrol of a bacterial histone deacetylase-like amidohydrolase (HDAH) from Bordetella/Alcaligenes strain FB188, which holds great potential to control deacetylation reactions of a broad spectrum of substrates in biotechnological and biomedical applications. Several HDAH variants with a single surface accessible cysteine close to the active site were developed and covalently modified by a monofunctional azobenzene-based photoswitch [4-phenylazomaleinanil (4-PAM)]. The enzymatic activity of three HDAH variants (M30C, S20C and M150C) were shown to be controlled by light. The thermal cis-to-trans relaxation of azobenzene conjugated to HDAH was up to 50-fold retarded compared to unbound 4-PAM allowing light pulse switching rather than continuing irradiation to maintain the thermodynamically less stable cis-state of covalently attached 4-PAM.
Acknowledgments
This work was supported by a grant of the hessian Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz (LOEWE Soft Control).
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Artikel in diesem Heft
- Masthead
- Masthead
- Reviews
- Physiological and pathological relevance of secretory microRNAs and a perspective on their clinical application
- Integration of stress signals by homeodomain interacting protein kinases
- Citrate – new functions for an old metabolite
- Research Articles/Short Communications
- Protein Structure and Function
- Azobenzene switch with a long-lived cis-state to photocontrol the enzyme activity of a histone deacetylase-like amidohydrolase
- Characterization of a type D1A EUL-related lectin from rice expressed in Pichia pastoris
- The legless lizard Anguis fragilis (slow worm) has a potent metal-responsive transcription factor 1 (MTF-1)
- Cell Biology and Signaling
- Effects of short-term chemical ablation of glucagon signalling by peptide-based glucagon receptor antagonists on insulin secretion and glucose homeostasis in mice
- A potent soluble epoxide hydrolase inhibitor, t-AUCB, modulates cholesterol balance and oxidized low density lipoprotein metabolism in adipocytes in vitro
- Activation of GPR119 by fatty acid agonists augments insulin release from clonal β-cells and isolated pancreatic islets and improves glucose tolerance in mice