Browsing by Author "Goede, Andrean"

The recent structural elucidation of about one dozen channels (in which we include transporters) has provided further evidence that these membrane proteins typically undergo large movements during their function. However, it is still not well understood how these proteins achieve the necessary trade-off between stability and mobility. To identify specific structural properties of channels, we compared the helix-packing and hydrogen-bonding patterns of channels with those of membrane coils; the latter is a class of membrane proteins whose structures are expected to be more rigid. We describe in detail how in channels, helix pairs are usually arranged in packing motifs with large crossing angles (vertical bar tau vertical bar approximate to 40 degrees), where the (small) side chains point away from the packing core and the backbones of the two helices are in close contact. We found that this contributes to a significant enrichment of C alpha-H center dot center dot center dot O bonds and to a packing geometry where right-handed parallel (tau = -40 degrees +/- 10 degrees) and anti-parallel (tau = +140 degrees +/- 25 degrees) arrangements are equally preferred. By sharp contrast, the interdigitation and hydrogen bonding of side chains in helix pairs of membrane coils results in narrowly distributed left-handed antiparallel arrangements with crossing angles tau = -160 degrees +/- 10 degrees (vertical bar tau vertical bar approximate to 200). In addition, we show that these different helix-packing modes of the two types of membrane proteins correspond to specific hydrogen-bonding patterns. In particular, in channels, three times as many of the hydrogen-bonded helix pairs are found in parallel right-handed motifs than are non-hydrogen-bonded helix pairs. Finally, we discuss how the presence of weak hydrogen bonds, water-containing cavities, and right-handed crossing angles may facilitate the required conformational flexibility between helix pairs of channels while maintaining sufficient structural stability.

The Superimpose webserver performs structural similarity searches with a preference towards 3D structure-based methods. Similarities can be detected between small molecules (e. g. drugs), parts of large structures (e. g. binding sites of proteins) and entire proteins. For this purpose, a number of algorithms were implemented and various databases are provided. Superimpose ' assists the user regarding the selection of a suitable combination of algorithm and database. After the computation on our server infrastructure, a visual assessment of the results is provided. The structure-based in silico screening for similar drug-like compounds enables the detection of scaffold-hoppers with putatively similar effects. The possibility to find similar binding sites can be of special interest in the functional analysis of proteins. The search for structurally similar proteins allows the detection of similar folds with different backbone topology. The Superimpose ' server is available at: http://bioinformatics.charite.de/superimpose.