5j75

Fluorogen Activating Progein AM2.2 in complex with ML342

spinqualitylabelsall models 5j75, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5j75 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 6GQ, PO4 Related: 5j74 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Publication Abstract from PubMed A new class of biosensors, fluorogen activating proteins (FAPs), has been successfully used to track receptor trafficking in live cells. Unlike the traditional fluorescent proteins (FPs), FAPs do not fluoresce unless bound to their specific small-molecule fluorogens, and thus FAP-based assays are highly sensitive. Application of the FAP-based assay for protein trafficking in high-throughput flow cytometry resulted in the discovery of a new class of compounds that interferes with the binding between fluorogens and FAP, thus blocking the fluorescence signal. These compounds are high-affinity, nonfluorescent analogs of fluorogens with little or no toxicity to the tested cells and no apparent interference with the normal function of FAP-tagged receptors. The most potent compound among these, N,4-dimethyl-N-(2-oxo-2-(4-(pyridin-2-yl)piperazin-1-yl)ethyl)benzenesulfonamide (ML342), has been investigated in detail. X-ray crystallographic analysis revealed that ML342 competes with the fluorogen, sulfonated thiazole orange coupled to diethylene glycol diamine (TO1-2p), for the same binding site on a FAP, AM2.2. Kinetic analysis shows that the FAP-fluorogen interaction is more complex than a homogeneous one-site binding process, with multiple conformational states of the fluorogen and/or the FAP, and possible dimerization of the FAP moiety involved in the process. Discovery of Small-Molecule Nonfluorescent Inhibitors of Fluorogen-Fluorogen Activating Protein Binding Pair.,Wu Y, Stauffer SR, Stanfield RL, Tapia PH, Ursu O, Fisher GW, Szent-Gyorgyi C, Evangelisti A, Waller A, Strouse JJ, Carter MB, Bologa C, Gouveia K, Poslusney M, Waggoner AS, Lindsley CW, Jarvik JW, Sklar LA J Biomol Screen. 2016 Jan;21(1):74-87. doi: 10.1177/1087057115609145. Epub 2015, Oct 6. PMID:26442911 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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