The making of a potent L-lactate transport inhibitor

Bosshart, Patrick D.; Kalbermatter, David; Bonetti, Sara; Fotiadis, Dimitrios (2021). The making of a potent L-lactate transport inhibitor. Communications chemistry, 4(1) Springer Nature 10.1038/s42004-021-00564-5

Preview

Text The_making_of_a_potent_L-lactate_transport_inhibit__1_.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (1MB) | Preview

L-lactate is an important metabolite, energy source, and signaling molecule in health and disease. In mammals, its transport across biological membranes is mediated by monocarboxylate transporters (MCTs) of the solute carrier 16 (SLC16) family. Malfunction, overexpression or absence of transporters of this family are associated with diseases such as cancer and type 2 diabetes. Moreover, lactate acts as a signaling molecule and virulence factor in certain bacterial infections. Here, we report the rational, structure-guided identification of potent, nanomolar affinity inhibitors acting on an L-lactate-specific SLC16 homologue from the bacterium Syntrophobacter fumaroxidans (SfMCT). High-resolution crystal structures of SfMCT with bound inhibitors uncovered their interaction mechanism on an atomic level and the role of water molecules in inhibitor binding. The presented systematic approach is a valuable procedure for the identification of L-lactate transport inhibitors. Furthermore, identified inhibitors represent potential tool compounds to interfere with monocarboxylate transport across biological membranes mediated by MCTs.

Interest & Impact

Downloads

56 since deposited on 20 Jan 2022
22 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item