6EUQ
MdfA(Q131R/L339E)
Summary for 6EUQ
| Entry DOI | 10.2210/pdb6euq/pdb |
| Descriptor | Multidrug transporter MdfA, nonyl beta-D-glucopyranoside, (3ALPHA,5BETA,12ALPHA)-3,12-DIHYDROXYCHOLAN-24-OIC ACID, ... (10 entities in total) |
| Functional Keywords | multidrug efflux protein, membrane protein, transport protein |
| Biological source | Escherichia coli (strain K12) |
| Total number of polymer chains | 1 |
| Total formula weight | 47596.24 |
| Authors | |
| Primary citation | Zomot, E.,Yardeni, E.H.,Vargiu, A.V.,Tam, H.K.,Malloci, G.,Ramaswamy, V.K.,Perach, M.,Ruggerone, P.,Pos, K.M.,Bibi, E. A New Critical Conformational Determinant of Multidrug Efflux by an MFS Transporter. J. Mol. Biol., 430:1368-1385, 2018 Cited by PubMed Abstract: Secondary multidrug (Mdr) transporters utilize ion concentration gradients to actively remove antibiotics and other toxic compounds from cells. The model Mdr transporter MdfA from Escherichia coli exchanges dissimilar drugs for protons. The transporter should open at the cytoplasmic side to enable access of drugs into the Mdr recognition pocket. Here we show that the cytoplasmic rim around the Mdr recognition pocket represents a previously overlooked important regulatory determinant in MdfA. We demonstrate that increasing the positive charge of the electrically asymmetric rim dramatically inhibits MdfA activity and sometimes even leads to influx of planar, positively charged compounds, resulting in drug sensitivity. Our results suggest that unlike the mutants with the electrically modified rim, the membrane-embedded wild-type MdfA exhibits a significant probability of an inward-closed conformation, which is further increased by drug binding. Since MdfA binds drugs from its inward-facing environment, these results are intriguing and raise the possibility that the transporter has a sensitive, drug-induced conformational switch, which favors an inward-closed state. PubMed: 29530612DOI: 10.1016/j.jmb.2018.02.026 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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