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PDBsum entry 4ubk
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References listed in PDB file
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Key reference
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Title
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Mapping the accessible conformational landscape of an insect carboxylesterase using conformational ensemble analysis and kinetic crystallography.
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Authors
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G.J.Correy,
P.D.Carr,
T.Meirelles,
P.D.Mabbitt,
N.J.Fraser,
M.Weik,
C.J.Jackson.
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Ref.
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Structure, 2016,
24,
977-987.
[DOI no: ]
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PubMed id
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Abstract
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The proper function of enzymes often depends upon their efficient
interconversion between particular conformational sub-states on a free-energy
landscape. Experimentally characterizing these sub-states is challenging, which
has limited our understanding of the role of protein dynamics in many enzymes.
Here, we have used a combination of kinetic crystallography and detailed
analysis of crystallographic protein ensembles to map the accessible
conformational landscape of an insect carboxylesterase (LcαE7) as it traverses
all steps in its catalytic cycle. LcαE7 is of special interest because of its
evolving role in organophosphate insecticide resistance. Our results reveal that
a dynamically coupled network of residues extends from the substrate-binding
site to a surface loop. Interestingly, the coupling of this network that is
apparent in the apoenzyme appears to be reduced in the phosphorylated enzyme
intermediate. Altogether, the results of this work highlight the importance of
protein dynamics to enzyme function and the evolution of new activity.
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