Solvent isotope effects and the nature of electrophilic catalysis m the action of the lactate dehydrogenase of bacillus stearothermophilus

Minli Xie; Javier Seravalli; W. Phillip Huskey; K. Barbara Schowen; Richard L. Schowen

doi:10.1016/0968-0896(94)85019-4

Solvent isotope effects and the nature of electrophilic catalysis m the action of the lactate dehydrogenase of bacillus stearothermophilus

Minli Xie, Javier Seravalli, W. Phillip Huskey, K. Barbara Schowen, Richard L. Schowen

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Deuterium oxide at atom fractions of deuterium from 0.0 to 0.97 has an effect of less than 20% on the kinetic term k_cat/K_mB (believed to reflect the transition state for the hydride-transfer step) for the reduction of pyruvic acid by NADH at 55 °C, with catalysis by the tetrameric form of the lactate dehydrogenase of Bacillus stearothermophilus. This observation suggests that the hydride-transfer event is not assisted by protonic bridging to the carbonyl group being reduced. The results are consistent with protonic bridging only if an opposing isotope effect is present, for example from a generalized conformation or solvation change. The results are consistent with other forms of electrophilic catalysis.

Original language	English (US)
Pages (from-to)	691-695
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry
Volume	2
Issue number	7
DOIs	https://doi.org/10.1016/0968-0896(94)85019-4
State	Published - Jul 1994
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/0968-0896(94)85019-4

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title = "Solvent isotope effects and the nature of electrophilic catalysis m the action of the lactate dehydrogenase of bacillus stearothermophilus",

abstract = "Deuterium oxide at atom fractions of deuterium from 0.0 to 0.97 has an effect of less than 20% on the kinetic term kcat/KmB (believed to reflect the transition state for the hydride-transfer step) for the reduction of pyruvic acid by NADH at 55 °C, with catalysis by the tetrameric form of the lactate dehydrogenase of Bacillus stearothermophilus. This observation suggests that the hydride-transfer event is not assisted by protonic bridging to the carbonyl group being reduced. The results are consistent with protonic bridging only if an opposing isotope effect is present, for example from a generalized conformation or solvation change. The results are consistent with other forms of electrophilic catalysis.",

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T1 - Solvent isotope effects and the nature of electrophilic catalysis m the action of the lactate dehydrogenase of bacillus stearothermophilus

AU - Xie, Minli

AU - Seravalli, Javier

AU - Huskey, W. Phillip

AU - Schowen, K. Barbara

AU - Schowen, Richard L.

PY - 1994/7

Y1 - 1994/7

N2 - Deuterium oxide at atom fractions of deuterium from 0.0 to 0.97 has an effect of less than 20% on the kinetic term kcat/KmB (believed to reflect the transition state for the hydride-transfer step) for the reduction of pyruvic acid by NADH at 55 °C, with catalysis by the tetrameric form of the lactate dehydrogenase of Bacillus stearothermophilus. This observation suggests that the hydride-transfer event is not assisted by protonic bridging to the carbonyl group being reduced. The results are consistent with protonic bridging only if an opposing isotope effect is present, for example from a generalized conformation or solvation change. The results are consistent with other forms of electrophilic catalysis.

AB - Deuterium oxide at atom fractions of deuterium from 0.0 to 0.97 has an effect of less than 20% on the kinetic term kcat/KmB (believed to reflect the transition state for the hydride-transfer step) for the reduction of pyruvic acid by NADH at 55 °C, with catalysis by the tetrameric form of the lactate dehydrogenase of Bacillus stearothermophilus. This observation suggests that the hydride-transfer event is not assisted by protonic bridging to the carbonyl group being reduced. The results are consistent with protonic bridging only if an opposing isotope effect is present, for example from a generalized conformation or solvation change. The results are consistent with other forms of electrophilic catalysis.

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Solvent isotope effects and the nature of electrophilic catalysis m the action of the lactate dehydrogenase of bacillus stearothermophilus

Abstract

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