| 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
|
|
WOS Category
|
CHEMISTRY, ORGANIC
|
| Resource |
| DNA material |
Genomic DNA of Pyrococcus furiosus JCM 8422T (JGD07704) |
| General Microbes |
JCM 8422 |
