TY - JOUR
T1 - Enzyme structure and dynamics affect hydrogen tunneling
T2 - The impact of a remote side chain (I553) in soybean lipoxygenase-1
AU - Meyer, Matthew P.
AU - Tomchick, Diana R.
AU - Klinman, Judith P.
PY - 2008/1/29
Y1 - 2008/1/29
N2 - This study examines the impact of a series of mutations at position 553 on the kinetic and structural properties of soybean lipoxygenase-1 (SLO-1). The previously uncharacterized mutants reported herein are I553L, I553V, and I553G. High-resolution x-ray studies of these mutants, together with the earlier studied I553A, show almost no structural change in relation to the WT-enzyme. By contrast, a progression in kinetic behavior occurs in which the decrease in the size of the side chain at position 553 leads to an increased importance of donor-acceptor distance sampling in the course of the hydrogen transfer process. These dynamical changes in behavior are interpreted in the context of two general classes of protein motions, preorganization and reorganization, with the latter including the distance sampling modes [Klinman JP (2006) Philos Trans R Soc London Ser B 361:1323-1331; Nagel Z, Klinman JP (2006) Chem Rev 106:3095-3118]. The aggregate data for SLO-1 show how judicious placement of hydrophobic side chains can influence enzyme catalysis via enhanced donor-acceptor hydrogenic wave function overlap.
AB - This study examines the impact of a series of mutations at position 553 on the kinetic and structural properties of soybean lipoxygenase-1 (SLO-1). The previously uncharacterized mutants reported herein are I553L, I553V, and I553G. High-resolution x-ray studies of these mutants, together with the earlier studied I553A, show almost no structural change in relation to the WT-enzyme. By contrast, a progression in kinetic behavior occurs in which the decrease in the size of the side chain at position 553 leads to an increased importance of donor-acceptor distance sampling in the course of the hydrogen transfer process. These dynamical changes in behavior are interpreted in the context of two general classes of protein motions, preorganization and reorganization, with the latter including the distance sampling modes [Klinman JP (2006) Philos Trans R Soc London Ser B 361:1323-1331; Nagel Z, Klinman JP (2006) Chem Rev 106:3095-3118]. The aggregate data for SLO-1 show how judicious placement of hydrophobic side chains can influence enzyme catalysis via enhanced donor-acceptor hydrogenic wave function overlap.
KW - Hydrogenic wave function overlap
KW - Protein dynamics
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U2 - 10.1073/pnas.0710643105
DO - 10.1073/pnas.0710643105
M3 - Article
C2 - 18216254
AN - SCOPUS:39549094013
SN - 0027-8424
VL - 105
SP - 1146
EP - 1151
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -