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BIO DESIGN

pISSN 2288-6982
eISSN 2288-7105

Insights into solute carriers as targets for cellular transp...

The field of substrate transport systems has grown steadily over the past decade and is now considered important for developing treatments to diseases. Human solute carriers (SLCs) consist of more than 420 different transporters, organized into 65 families (http://slc.bioparadigms.org/) according to sequence homology and transport functions. SLCs mediate the movement of ions, drugs, and metabolites across cell membranes, and dysfunction is associated with various diseases such as diabetes, cancer, and central nervous system (CNS) disorders. Thus, SLCs are emerging as important targets for therapeutic intervention and drug discovery. Despite their importance, sequence and structural information on SLCs is lacking, but recent biochemical and computational advances have expanded our understanding of SLC pharmacology. In particular, structures of SLCs elucidated by X-ray crystallography and cryo-electron microscopy (EM) have facilitated structure-based ligand prediction, comparison and modeling of SLC transporters, and virtual screening of small molecule libraries. Most available SLC structures are from prokaryotes, all SLC structures are classified into four major groups based on protein fold, and major facilitator superfamily (MFS) and leucine transporters (LeuT) have received most attention. This review systematically analyses the structures of different SLCs, and their molecular mechanisms of action and substrate recognition. Understanding drug-transporter interactions at the molecular level is essential for designing drugs with optimal therapeutic effects. Finally, we summarize the latest research trends, applications and computational approaches to developing solutes selectivity and inhibitors, including modelling techniques focused on the structure-based drug design for human SLC transporters.
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Vol.8 No.1 | March 30, 2020
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Aims and Scope

The journal Biodesign aims to promote the emerging research fields of designer biology that is based on the structural and functional analysis of biological phenomena. The journal emphasizes odification and improvement of biological substances as well as original analysis of biological structure and function.

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