4L1S

Covalent modification of transthyretin K15 by yielding the fluorescent conjugate (E)-3-(dimethylamino)-5-(4-hydroxy-3,5-dimethylstyryl)benzamide

Summary for 4L1S

• Entry DOI: 10.2210/pdb4l1s/pdb
• Related: 4FI6 4L1T
• Descriptor: Transthyretin, S-(4-fluorophenyl) 3-(dimethylamino)-5-[(E)-2-(4-hydroxy-3,5-dimethylphenyl)ethenyl]benzenecarbothioate (3 entities in total)
• Functional Keywords: hormone transport protein, thyroxine, retinol, transport protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P02766
• Total number of polymer chains: 2
• Total formula weight: 28397.77

Authors

Connelly, S.,Wilson, I.A. (deposition date: 2013-06-03, release date: 2013-10-02, Last modification date: 2024-10-16)

Primary citation

Baranczak, A.,Connelly, S.,Liu, Y.,Choi, S.,Grimster, N.P.,Powers, E.T.,Wilson, I.A.,Kelly, J.W.
Fluorogenic small molecules requiring reaction with a specific protein to create a fluorescent conjugate for biological imaging-what we know and what we need to learn.
Biopolymers, 101:484-495, 2014

PubMed Abstract: We seek fluorogenic small molecules that generate a fluorescent conjugate signal if and only if they react with a given protein-of-interest (i.e., small molecules for which noncovalent binding to the protein-of-interest is insufficient to generate fluorescence). Consequently, it is the new chemical entity afforded by the generally irreversible reaction between the small molecule and the protein-of-interest that enables the energy of an electron occupying the lowest unoccupied molecular orbital (LUMO) of the chromophore to be given off as a photon instead of being dissipated by nonradiative mechanisms in complex biological environments. This category of fluorogenic small molecules is created by starting with environmentally sensitive fluorophores that are modified by an essential functional group that efficiently quenches the fluorescence until a chemoselective reaction between that functional group and the protein-of-interest occurs, yielding the fluorescent conjugate. Fluorogenic small molecules are envisioned to be useful for a wide variety of applications, including live cell imaging without the requirement for washing steps and pulse-chase kinetic analyses of protein synthesis, trafficking, degradation, etc.

PubMed: 24105107
DOI: 10.1002/bip.22407

Experimental method

X-RAY DIFFRACTION (1.5 Å)