Mirror-image packing in enantiomer discrimination molecular basis for the enantioselectivity of B.cepacia lipase toward 2-methyl-3-phenyl-1-propanol.
Synthetic chemists often exploit the high enantioselectivity of lipases to prepare pure enantiomers of primary alcohols, but the molecular basis for this enantioselectivity is unknown. The crystal structures of two phosphonate transition-state analogs bound to Burkholderia cepacia lipase reveal this molecular basis for a typical primary alcohol: 2-methyl-3-phenyl-1-propanol. The enantiomeric alcohol moieties adopt surprisingly similar orientations, with only subtle differences that make it difficult to predict how to alter enantioselectivity. These structures, along with a survey of previous structures of enzyme bound enantiomers, reveal that binding of enantiomers does not involve an exchange of two substituent positions as most researchers assumed. Instead, the enantiomers adopt mirror-image packing, where three of the four substituents at the stereocenter lie in similar positions. The fourth substituent, hydrogen, points in opposite directions.
Mezzetti
Alessandra
A
Department of Chemistry, McGill University, Montréal, Québec H3A 2K6, Canada.
Schrag
Joseph D
JD
Cheong
Chan Seong
CS
Kazlauskas
Romas J
RJ
D016956:Burkholderia cepacia / Q000201:enzymology*; D003460:Crystallization; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D006868:Hydrolysis; D007202:Indicators and Reagents; D007700:Kinetics; D008024:Ligands; D008049:Lipase / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D020005:Propanols / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D013237:Stereoisomerism
C502969:2-methyl-3-phenyl-1-propanol; D007202:Indicators and Reagents; D008024:Ligands; D020005:Propanols; D008049:Lipase