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Mechanistic basis of L-lactate transport in the SLC16 solute carrier family

Nat Commun.. 2019-06; 
Bosshart PD, Kalbermatter D, Bonetti S, Fotiadis D
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Gene Services The gene of a major facilitator superfamily-type transporter from Syntrophobacter fumaroxidans (SfMCT, UniProt ID code A0LNN5) was synthesized codon-optimized for expression in E. coli (GenScript, Supplementary Table 2). SfMCT was ligated into the pZUDF21-rbs-3C-10His vector31 using 5’-HindIII and 3’-XhoI restriction sites for overexpression, or into the pEXT20 vector32 using 5’-EcoRI and 3’-XhoI restriction sites for functional studies. Get A Quote
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摘要

In human and other mammalian cells, transport of L-lactate across plasma membranes is mainly catalyzed by monocarboxylate transporters (MCTs) of the SLC16 solute carrier family. MCTs play an important role in cancer metabolism and are promising targets for tumor treatment. Here, we report the crystal structures of an SLC16 family homologue with two different bound ligands at 2.54 and 2.69 Å resolution. The structures show the transporter in the pharmacologically relevant outward-open conformation. Structural information together with a detailed structure-based analysis of the transport function provide important insights into the molecular working mechanisms of ligand binding and L-lactate transport

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