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PDBsum entry 5e5j
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Hydrolase/hydrolase inhibitor
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PDB id
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5e5j
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References listed in PDB file
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Key reference
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Title
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Long-Range electrostatics-Induced two-Proton transfer captured by neutron crystallography in an enzyme catalytic site.
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Authors
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O.Gerlits,
T.Wymore,
A.Das,
C.H.Shen,
J.M.Parks,
J.C.Smith,
K.L.Weiss,
D.A.Keen,
M.P.Blakeley,
J.M.Louis,
P.Langan,
I.T.Weber,
A.Kovalevsky.
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Ref.
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Angew Chem Int Ed Engl, 2016,
55,
4924-4927.
[DOI no: ]
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PubMed id
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Abstract
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Neutron crystallography was used to directly locate two protons before and after
a pH-induced two-proton transfer between catalytic aspartic acid residues and
the hydroxy group of the bound clinical drug darunavir, located in the catalytic
site of enzyme HIV-1 protease. The two-proton transfer is triggered by
electrostatic effects arising from protonation state changes of surface residues
far from the active site. The mechanism and pH effect are supported by quantum
mechanics/molecular mechanics (QM/MM) calculations. The low-pH proton
configuration in the catalytic site is deemed critical for the catalytic action
of this enzyme and may apply more generally to other aspartic proteases.
Neutrons therefore represent a superb probe to obtain structural details for
proton transfer reactions in biological systems at a truly atomic level.
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