New imine-reducing enzymes from β-hydroxyacid dehydrogenases by single amino acid substitutions.

We report the exploration of the evolutionary relationship between imine reductases (IREDs) and other dehydrogenases. This approach is informed by the sequence similarity between these enzyme families and the recently described promiscuous activity of IREDs for the highly reactive carbonyl compound 2,2,2-trifluoroacetophenone. Using the structure of the R-selective IRED from Streptosporangium roseum (R-IRED-Sr) as a model, β-hydroxyacid dehydrogenases (βHADs) were identified as the dehydrogenases most similar to IREDs.

Percolation in protein sequence space.

The currently known protein sequences are not distributed equally in sequence space, but cluster into families. Analyzing the cluster size distribution gives a glimpse of the large and unknown extant protein sequence space, which has been explored during evolution. For six protein superfamilies with different fold and function, the cluster size distributions followed a power law with slopes between 2.

Molecular Surface Maps.

We present Molecular Surface Maps, a novel, view-independent, and concise representation for molecular surfaces. It transfers the well-known world map metaphor to molecular visualization. Our application maps the complex molecular surface to a simple 2D representation through a spherical intermediate, the Molecular Surface Globe.

Network Analysis of Sequence-Function Relationships and Exploration of Sequence Space of TEM β-Lactamases.

The Lactamase Engineering Database (www.LacED.uni-stuttgart.

Identification of imine reductase-specific sequence motifs.

Chiral amines are valuable building blocks for the production of a variety of pharmaceuticals, agrochemicals and other specialty chemicals. Only recently, imine reductases (IREDs) were discovered which catalyze the stereoselective reduction of imines to chiral amines. Although several IREDs were biochemically characterized in the last few years, knowledge of the reaction mechanism and the molecular basis of substrate specificity and stereoselectivity is limited.

Enzyme toolbox: novel enantiocomplementary imine reductases.

Reducing reactions are among the most useful transformations for the generation of chiral compounds in the fine-chemical industry. Because of their exquisite selectivities, enzymatic approaches have emerged as the method of choice for the reduction of C=O and activated C=C bonds. However, stereoselective enzymatic reduction of C=N bonds is still in its infancy-it was only recently described after the discovery of enzymes capable of imine reduction.