ArticleBiochemistry2010
Simulation of spontaneous substrate binding revealing the binding pathway and mechanism and initial conformational response of GlpT.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 40 citations in OpenAlex.
- Transporter characterisation reveals aminoethylphosphonate mineralisation as a key step in the marine phosphorus redox cycle.Nature communications · 2021Article
- Microscopic Characterization of Membrane Transporter Function by In Silico Modeling and Simulation.Methods in enzymology · 2016Review
- Atomic-level characterization of transport cycle thermodynamics in the glycerol-3-phosphate:phosphate antiporter.Nature communications · 2015Article
- Closure of the cytoplasmic gate formed by TM5 and TM11 during transport in the oxalate/formate exchanger from Oxalobacter formigenes.Biochemistry · 2014Article
- Flexible gates generate occluded intermediates in the transport cycle of LacY.Journal of molecular biology · 2014Article
- Protonation drives the conformational switch in the multidrug transporter LmrP.Nature chemical biology · 2014Article
- Transient formation of water-conducting states in membrane transporters.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Visualizing functional motions of membrane transporters with molecular dynamics simulations.Biochemistry · 2013Review
- Proton-coupled dynamics in lactose permease.Structure (London, England : 1993) · 2012Article
- Article
- Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Article
- The substrate-driven transition to an inward-facing conformation in the functional mechanism of the dopamine transporter.PloS one · 2011Article
- Probing the periplasmic-open state of lactose permease in response to sugar binding and proton translocation.Journal of molecular biology · 2010Article
- Modeling and dynamics of the inward-facing state of a Na+/Cl- dependent neurotransmitter transporter homologue.PLoS computational biology · 2010Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Glycerol 3-phosphate transporter (GlpT) mediates the import of glycerol 3-phosphate (G3P) using the gradient of inorganic phosphate (P(i)). To study the process and mechanism of substrate binding and to investigate the protein's initial response, we performed equilibrium simulations of wild-type GlpT and several of its mutant forms in membranes in the presence of all physiologically relevant substrates (P(i)(-), P(i)(2-), G3P(-), and G3P(2-)). The simulations capture spontaneous substrate binding of GlpT, driven by the positive electrostatic potential of the lumen. K80 is found to act as a "hook" making the first encounter with the substrate and guiding it toward the binding site, where it binds tightly to R45, a key binding site residue that acts as a "fork" holding the substrate. R269 establishes no direct contact with the substrate during the simulations, a surprising behavior given its structural pseudosymmetry to R45. In all substrate-bound systems, partial closing of the cytoplasmic half of GlpT was observed. The substrate appears to stabilize the partially occluded state, as in the two apo simulations either no closing was observed or the protein reverted to its open form toward the end of the simulation, whereas in all substrate-bound systems, a stable partially closed state was produced. Along with the modulation of the periplasmic salt bridge network, these substrate-induced events destabilize the periplasmic half while inducing a closure in the cytoplasmic half, thus capturing the early stages of the proposed rocker-switch mechanism in GlpT.
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