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Molecular mechanism of ligand recognition by the Mhp1 transporter

Molecular mechanism of ligand recognition by the Mhp1 transporter

The hydantoin transporter Mhp1 is a sodium?coupled secondary active transport protein of the nucleobase?cation?symport family and shares the widespread 5?helix inverted repeat transporter architecture. Our previous work showed Mhp1 functions according to the alternating access mechanism. In our new paper in EMBO J , we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site?directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands.

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Flexible Gates Generate Occluded Intermediates in the Transport Cycle of LacY

Flexible Gates Generate Occluded Intermediates in the Transport Cycle of LacY

We show that one of the best-studied secondary active transporters, the lactose permease LacY, goes through an occluded conformation during its transport cycle. We propose an atomically detailed model of the apo-occluded state. The simulations predict the formation of a transient salt bridge that has been hypothesized in the canonical model for transport of LacY. The simulations are validated by comparison to experimental EPR DEER data, using a new approach to simulate spin-label distance distributions through post-processing of molecular dynamics trajectories. We also define a set of order parameters that consistently classify all known MFS transporter structures as outward-open, occluded, or inward-open conformations.

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A two-domain elevator mechanism for sodium/proton antiport

A two-domain elevator mechanism for sodium/proton antiport

In a combined X-ray crystallography/biochemistry/molecular simulation study published in Nature we present the structure of the sodium/proton antiporter NapA in its outward facing conformation. Together with the inward facing conformation of the related transporter NhaA we can now understand the conformational changes required for the sodium/proton antiport mechanism.

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