Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Azobenzene switch with a long-lived cis-state to photocontrol the enzyme activity of a histone deacetylase-like amidohydrolase. 2426 48

Base editors (BEs) are RNA-guided CRISPR-Cas-derived genome editing tools that induce single-nucleotide changes. The limitations of current BEs lie in their low precision (especially when multiple target nucleotides of the deaminase are present within the activity window) and their restriction to targets that are in proper distance from the PAM sequence. We have recently developed high-precision cytidine BEs by engineering CDA1 truncations and nCas9 fusions that predominantly edit nucleotide C-18 relative to the PAM sequence NGG. Here, by testing fusions with Cas9 variants that recognize alternative PAMs, we provide a series of high-precision BEs that greatly expand the versatility of base editing. In addition, we obtained BEs that selectively edit C-15 or C-16. We also show that our high-precision BEs can substantially reduce off-target effect. These improved base editing tools will be widely applicable in basic research, biotechnology and gene therapy.
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PMID:Expanding the genome-targeting scope and the site selectivity of high-precision base editors. 3200 20