RRC ID 29446
Author Hipolito CJ, Tanaka Y, Katoh T, Nureki O, Suga H.
Title A macrocyclic peptide that serves as a cocrystallization ligand and inhibits the function of a MATE family transporter.
Journal Molecules
Abstract The random non-standard peptide integrated discovery (RaPID) system has proven to be a powerful approach to discover de novo natural product-like macrocyclic peptides that inhibit protein functions. We have recently reported three macrocyclic peptides that bind to Pyrococcus furiosus multidrug and toxic compound extrusion (PfMATE) transporter and inhibit the transport function. Moreover, these macrocyclic peptides were successfully employed as cocrystallization ligands of selenomethionine-labeled PfMATE. In this report, we disclose the details of the RaPID selection strategy that led to the identification of these three macrocyclic peptides as well as a fourth macrocyclic peptide, MaD8, which is exclusively discussed in this article. MaD8 was found to bind within the cleft of PfMATE's extracellular side and blocked the path of organic small molecules being extruded. The results of an ethidium bromide efflux assay confirmed the efflux inhibitory activity of MaD8, whose behavior was similar to that of previously reported MaD5.
Volume 18(9)
Pages 10514-30
Published 2013-8-30
DOI 10.3390/molecules180910514
PII molecules180910514
PMID 23999725
PMC PMC6270235
MeSH Amino Acid Sequence Antiporters / antagonists & inhibitors Antiporters / chemistry* Archaeal Proteins / antagonists & inhibitors Archaeal Proteins / chemistry* Crystallization Crystallography, X-Ray Drug Discovery Drug Resistance, Multiple Escherichia coli Ethidium / metabolism Fluorescent Dyes / metabolism Ligands Models, Molecular Molecular Sequence Data Peptides, Cyclic / chemistry Peptides, Cyclic / pharmacology* Protein Binding Protein Structure, Secondary Pyrococcus furiosus / metabolism*
IF 3.267
Times Cited 32
DNA material Genomic DNA of Pyrococcus furiosus JCM 8422T (JGD07704)
General Microbes JCM 8422