Predicting the solvent dependence of enzymatic substrate specificity using semiempirical thermodynamic calculations

Journal Article · Wed Nov 03 00:00:00 EST 1993 · Journal of the American Chemical Society; (United States)

DOI:https://doi.org/10.1021/ja00075a063· OSTI ID:5105592

Wescott, C R; Klibanov, A M ^[1]

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1. Massachusetts Inst. of Technology, Cambridge, MA (United States)

The discovery that substrate specificity of enzymes is markedly dependent on the solvent has prompted a search for a mechanistic explanation of this phenomenon. Recently, we have succeeded in rationalizing the observed solvent effect on the transesterification reactions of N-Ac-L-Ser-OEt (Ser) and N-Ac-L-Phe-OEt (Phe) with 1-propanol catalyzed by the protease subtilisin Carlsberg. A mathematical equation has been derived which relates the substrate specificity in an organic solvent to that in water and to the solvent-to-water partition coefficients (P) of the substrates. A fundamental limitation of this approach, however, is that it can be used only with water-immiscible solvents, because direct measurements of partition coefficients between water and water-miscible solvents are not feasible. In principle, our approach is independent of the enzyme and this should be of general significance. This fact, combined with the ability to calculate the P ratios of substrates by computer, allows the quantitative prediction of enzymatic specificity for various enzyme/substrate systems in any solvent, given the substrate specificity in a single reference solvent (e.g., in water, as herein). 11 refs., 1 fig., 1 tab.

• OSTI ID: 5105592
• Journal Information: Journal of the American Chemical Society; (United States), Vol. 115:22; ISSN 0002-7863
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
CHEMICAL REACTIONS
COMPUTERIZED SIMULATION
THERMODYNAMICS
ENZYMES
COMPILED DATA
MATHEMATICAL MODELS
PARTITION
SOLVENTS
SUBSTRATES
WATER
DATA
HYDROGEN COMPOUNDS
INFORMATION
NUMERICAL DATA
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PROTEINS
SIMULATION
550200* - Biochemistry
990200 - Mathematics & Computers