journal menu
![[Figure 7]](qe5012fig7mag.jpg)
|
|
Figure 7
(a) Schematic illustration of the substrate-transport pathway by MmpL3 based on high-resolution structural analysis. The hydrophobic surface of the substrate-binding pocket formed between the two periplasmic domains (PN and PC) is shown in red. The important residues aspartic acid (D) and tyrosine (Y) in the TM domain, which are involved in proton translocation across the membrane, are depicted as a D–Y pair. Four binding sites are shown (named sites 1, 2, 3 and 4), based on the position of the LMT binding site observed in our crystal structure. The steps of transport, including the extraction of the substrate from the membrane (1) and its transport into the periplasmic binding pocket (2), and then the exit pathway with flip-flop (3), are numbered. (b) One of the largest binding sites is reported together with the GRID MIF: two units of LMT are partially aligned over hydrophilic (polar moiety) and hydrophobic (alkyl chain) MIFs, reported with cyan and yellow isocontour surfaces, obtained by using the probes OH2 (−8.0 kcal mol−1) and CRY (−1.4 kcal mol−1), respectively. (c) The main binding site of MmpL3, where UPAR-1109 binds, has both hydrophobic and polar hotspots; the hydrophobicity is mostly in subsites S3 and S5, whereas the polar hotspots are in subsite S4, where there is evidence of the good overlap between the water molecules (red) from the X-ray structure and the corresponding GRID MIF (probe OH2, reported in cyan). |
![[Figure 7]](qe5012fig7.jpg)
 | STRUCTURAL BIOLOGY |
ISSN: 2059-7983
access
