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Title: Structural basis for the role of LYS220 as proton donor for nucleotidyl transfer in HIV-1 reverse transcriptase
Authors: Michielssens, Servaas ×
Moors, Sam
Froeyen, Mathy
Herdewijn, Piet
Ceulemans, Arnout #
Issue Date: Aug-2011
Publisher: North-Holland Pub. Co.
Series Title: Biophysical Chemistry vol:157 issue:1-3 pages:1-6
Abstract: Biochemical studies by Castro et al. have recently revealed a crucial role for a general acid in the catalysis of nucleic acid transfer in distinct classes of polymerases. For HIV-RT LYS220 was identified as proton donor. This was unanticipated from a structural point of view, since in all ternary crystal structures of HIV-RT LYS220 are too distant from the active site to fulfill this role. In this work molecular dynamics simulations were used to reveal the dynamics of HIV-RT and to provide structural evidence for the role of LYS220. During a 1μs molecular dynamics simulation LYS220 migrates toward the active site and occupies several positions enabling direct and water mediated proton transfer towards pyrophosphate. A combination of quantum mechanical and molecular mechanics methods was used to validate the different modes of interaction.
URI: 
ISSN: 0301-4622
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
Quantum Chemistry and Physical Chemistry Section
Department of Pharmaceutical & Pharmacological Sciences - miscellaneous
× corresponding author
# (joint) last author

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