Enzyme Principles

Structural Principles in the Development of Cyclic Peptidic Enzyme Inhibitors

This review summarizes our studies in the development of small cyclic peptides for specifically modulating enzyme activity. Serine proteases share highly similar active sites but perform diverse physiological and pathological functions. From a phage-display peptide library, we isolated two mono-cyclic peptides, upain-1 (CSWRGLENHRMC) and mupain-1 (CPAYSRYLDC), which inhibit the activity of huma...

Simplifying principles for chemical and enzyme reaction kinetics.

Tihonov's Theorems for systems of first-order ordinary differential equations containing small parameters in the derivatives, which form the mathematical foundation of the steady-state approximation, are restated. A general procedure for simplifying chemical and enzyme reaction kinetics, based on the difference of characteristic time scales, Is presented. Korzuhin's Theorem, which makes it poss...

Evolutionary-Economic Principles as Regulators of Soil Enzyme Production and Ecosystem Function

Extracellular enzymes are ubiquitous in soil environments. Produced by microorganisms and plant roots, these enzymes serve a dual function of degrading complex organic material into simpler forms and acquiring resources for the enzyme producer (Burns 1982; Sinsabaugh 1994). Without extracellular enzymes, microbes and plants would be unable to obtain resources from complex compounds, and cycles ...

From Molecular Phylogenetics to Quantum Chemistry: Discovering Enzyme Design Principles through Computation

Design principles of autocatalytic cycles constrain enzyme kinetics and force over-expression at flux branch points

A set of chemical reactions that require a metabolite to synthesize more of that metabolite is an autocatalytic cycle. Such metabolic designs must meet specific conditions to support stable fluxes, hence avoiding depletion of intermediate metabolites. Here we show that most of the reactions in central carbon metabolism are part of compact autocatalytic cycles. As such, they are subjected to con...