Molecular Dynamics Simulations of Selective Metabolite
Transport across the Propanediol Bacterial Microcompartment Shell
Posted on 2017-08-22 - 19:35
Bacterial microcompartments
are giant protein-based organelles
that encapsulate special metabolic pathways in diverse bacteria. Structural
and genetic studies indicate that metabolic substrates enter these
microcompartments by passing through the central pores in hexameric
assemblies of shell proteins. Limiting the escape of toxic metabolic
intermediates created inside the microcompartments would confer a
selective advantage for the host organism. Here, we report the first
molecular dynamics (MD) simulation studies to analyze small-molecule
transport across a microcompartment shell. PduA is a major shell protein
in a bacterial microcompartment that metabolizes 1,2-propanediol via
a toxic aldehyde intermediate, propionaldehyde. Using both metadynamics
and replica-exchange umbrella sampling, we find that the pore of the
PduA hexamer has a lower energy barrier for passage of the propanediol
substrate compared to the toxic propionaldehyde generated within the
microcompartment. The energetic effect is consistent with a lower
capacity of a serine side chain, which protrudes into the pore at
a point of constriction, to form hydrogen bonds with propionaldehyde
relative to the more freely permeable propanediol. The results highlight
the importance of molecular diffusion and transport in a new biological
context.
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Park, Jiyong; Chun, Sunny; A. Bobik, Thomas; Houk, Kendall N.; Yeates, Todd O. (2017). Molecular Dynamics Simulations of Selective Metabolite
Transport across the Propanediol Bacterial Microcompartment Shell. ACS Publications. Collection. https://doi.org/10.1021/acs.jpcb.7b07232
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AUTHORS (5)
JP
Jiyong Park
SC
Sunny Chun
TA
Thomas A. Bobik
KH
Kendall N. Houk
TY
Todd O. Yeates
KEYWORDS
hexameric assembliesMolecular Dynamics Simulationsreplica-exchange umbrella samplingporegiant protein-based organellesform hydrogen bondssmall-molecule transportPduA hexamershell proteinspropionaldehydeserine side chainMicrocompartment Shellpropanediol substrateMDsimulation studiesenergy barriershell proteinhost organismmicrocompartment shellSelective Metabolite Transport