Figure 6

Docking analysis of hLAT1. Docking analysis in site 1 of hLAT1. The cryo-EM structure of hLAT1 in inward conformation (PDB ID: 6IRT, chain B) was represented as ribbon (sky blue) using Chimera v.1.7 software (https://www.cgl.ucsf.edu/chimera). Docking analysis was performed using InducedFit docking from Schrödinger-Maestro v11.3⁶⁵ as described in “Methods”. In (a), molecular docking of cholesterol (in salmon) in the site 1 (TM 1a, TM5 and TM7). Residues belonging to cholesterol site are represented as sticks. This pose has a docking score of -5.54 and a MMGBSA binding energy of − 46.66 kcal/mol. The membrane and intracellular/extracellular environment are indicated. In (b), molecular docking of ATP in site 1 in the presence of cholesterol. The best pose from cholesterol docking was used to dock ATP. Lys 204 represented in stick makes an electrostatic bond (in violet) with the γ-phosphate of ATP. This pose has a docking score of − 6.92 and a MMGBSA binding energy of − 8.97 kcal/mol. In (c), 2D visualization of hLAT1 interaction with ATP. The arrows indicated the residues involved in the binding of ATP. In (d), molecular docking of ATP in site 1 in the absence of cholesterol; in violet, electrostatic bond with Lys 204 represented in stick. The pose has a docking score of − 6.336.