5vnp
From Proteopedia
X-ray crystal structure of Halotag bound to the P1 benzoxadiazole fluorogenic ligand
Structural highlights
FunctionDHAA_RHORH Catalyzes hydrolytic cleavage of carbon-halogen bonds in halogenated aliphatic compounds, leading to the formation of the corresponding primary alcohols, halide ions and protons. Expresses halogenase activity against 1-chloroalkanes of chain length C3 to C10, and also shows a very weak activity with 1,2-dichloroethane. Publication Abstract from PubMedDrug-induced proteome stress that involves protein aggregation may cause adverse effects and undermine the safety profile of a drug. Safety of drugs is regularly evaluated using cytotoxicity assays that measure cell death. However, these assays provide limited insights into the presence of proteome stress in live cells. A fluorogenic protein sensor is reported to detect drug-induced proteome stress prior to cell death. An aggregation prone Halo-tag mutant (AgHalo) was evolved to sense proteome stress through its aggregation. Detection of such conformational changes was enabled by a fluorogenic ligand that fluoresces upon AgHalo forming soluble aggregates. Using 5 common anticancer drugs, we exemplified detection of differential proteome stress before any cell death was observed. Thus, this sensor can be used to evaluate drug safety in a regime that the current cytotoxicity assays cannot cover and be generally applied to detect proteome stress induced by other toxins. AgHalo: A Facile Fluorogenic Sensor to Detect Drug-Induced Proteome Stress.,Liu Y, Fares M, Dunham NP, Gao Z, Miao K, Jiang X, Bollinger SS, Boal AK, Zhang X Angew Chem Int Ed Engl. 2017 Jul 17;56(30):8672-8676. doi:, 10.1002/anie.201702417. Epub 2017 Jun 19. PMID:28557281[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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