jz0c00547_si_001.pdf (1.6 MB)
Free Energy Analysis of a Conformational Change of Heme ABC Transporter BhuUV‑T
journal contribution
posted on 2020-03-27, 11:03 authored by Koichi Tamura, Yuji SugitaThe heme ATP-binding cassette (ABC)
transporter BhuUV-T of bacterial
pathogen Burkholderia cenocepacia is required to
transport heme across the inner cell membrane. The current hypothesis
is that the binding of two ATPs to the nucleotide-binding domains
of the transporter drives the initial steps of the transport cycle
in
which the empty transport sites are reoriented from the cytosol to
the periplasm. Molecular details are missing because the structure
of a key occluded intermediate remains hypothetical. Here we perform
molecular simulations to analyze the free energy surface (FES) of
the first step of the reorientation, namely the transition from an
open inward-facing (IF) transport site to an occluded (Occ) conformation.
We have modeled the latter structure in silico in
a previous study. A simple annealing procedure removes residual bias
originating from non-equilibrium targeted molecular dynamics. The
calculated FES reveals the role of the ATPs in inducing the IF →
Occ conformational change and validates the modeled Occ
conformation.
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inner cell membranefree energy surfacefree energy analysisperform molecular simulationsempty transport sitesburkholderia cenocepacia transport heme acrosscalculated fes revealsmodeled occ conformationtransport sitetransport cyclesilico molecular detailsheme atptransporter drivestransporter bhuuvprevious studyopen inwardinitial stepsfirst stepcurrent hypothesisconformational changebacterial pathogen
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