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Photoactivatable Myristic Acid Probes for UNC119‐Cargo Interactions
Author(s) -
Kaiser Nadine,
Mejuch Tom,
Fedoryshchak Roman,
Janning Petra,
Tate Edward W.,
Waldmann Herbert
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800406
Subject(s) - myristoylation , myristic acid , chemistry , biochemistry , covalent bond , pegylation , chaperone (clinical) , peptide , protein–protein interaction , biophysics , membrane , biology , fatty acid , medicine , organic chemistry , polyethylene glycol , pathology , palmitic acid
Protein myristoylation plays key roles in biological processes, for instance, in membrane attachment and activation of proteins and in mediating protein–protein and protein–lipid interactions. Furthermore, myristoylated proteins are involved in disorders, including cancer and viral infections. Therefore, new tools to study protein myristoylation are in high demand. Herein, we report the development of photoactivatable probes, based on a diazirine‐substituted analogue of myristic acid. The probes bind to and, upon irradiation, covalently label the lipid‐binding chaperone protein uncoordinated 119 (UNC119). UNC119 increases overall solubility and regulates specifically the transport of myristoylated proteins between intercellular membranes. The binding mode of the probes is similar to that of the myristate moiety, and the residues inside the hydrophobic pocket of UNC119 proteins that are critical for covalent binding have been identified. The interaction with UNC119 was also demonstrated in cell lysate by means of affinity enrichment. Moreover, it is shown that the myristate analogue can be incorporated into peptide substrates by N ‐myristoyl transferases of Leishmania and Trypanosoma protozoan parasites.