Moving Through Barriers in Science and Life

Abstract

This first serious attempt at an autobiographical accounting has forced me to sit still long enough to compile my thoughts about a long personal and scientific journey. I especially hope that my trajectory will be of interest and perhaps beneficial to much younger women who are just getting started in their careers. To paraphrase from Virginia Woolf's writings in A Room of One's Own at the beginning of the 20th century, “for most of history Anonymous was a Woman.” However, Ms. Woolf is also quoted as saying “nothing has really happened until it has been described,” a harbinger of the enormous historical changes that were about to be enacted and recorded by women in the sciences and other disciplines. The progress in my chosen field of study—the chemical basis of enzyme action—has also been remarkable, from the first description of an enzyme's 3D structure to a growing and deep understanding of the origins of enzyme catalysis.

Structural basis of the pleiotropic and specific phenotypic consequences of missense mutations in the multifunctional NAD(P)H:quinone oxidoreductase 1 and their pharmacological rescue

“…KIEs and activation parameters serve to prove the nature of the chemical step and the effects of mutations on the structural organization and dynamics at the active site during catalysis [ 47 , 48 ]. For the fast FAD reduction step in all three variants, KIEs are temperature independent and above unity.…”

The Catalytic Cycle of the Antioxidant and Cancer-Associated Human NQO1 Enzyme: Hydride Transfer, Conformational Dynamics and Functional Cooperativity

“…KIEs usually exhibit maximal values at lower temperatures, suggesting this might be a nearly limiting value. The magnitude of primary H/D KIEs theoretically can reach a maximum value of 8, although there are considerably larger values reported for some enzymes [78]. Nonetheless, primary KIEs can also decrease towards 1 when the C-H bond is either broken less (i.e., earlier transition state) or more (i.e., later transition state) in the transition state structure (asymmetrical), or if the transition state is nonlinear [79,80].…”

Large Isotope Effects in Organometallic Chemistry

“…[10,[12][13][14][15][16][17]72] Experimental evidence for proton tunneling has been collected (and also debated) in an array of chemical fields, particularly enzymology and physical organic chemistry. [19,73,74] Within synthetic organometallic chemistry, the temperature dependence of rates and KIEs has been used both to support a tunneling pathway [39][40][41]50,49] and to rule out tunneling. [64,69] Kinetic analysis under different reaction conditions is used to support non-tunneling explanations (b) and (c) for large observed isotope effects, especially when an isotope effect is found to change under different measurement conditions.…”