A strained N-capping motif in α-helices of ßαß-units.

A novel helical N-capping motif has been considered. It occurs in the ßα-arches of right-handed ßαß-units and contains an N-cap residue in a sterically strained conformation. Moreover, this amino acid position contains almost no glycines, that could relieve strain. It was shown that the N-cap adopts this conformation as a result of the unusual convergence between the second and third amino acid positions of the α-helix (counting from the N-cap) and the second position of the preceding ß-strand. This is achieved by the presence of glycines in the specified positions (i.e. positions i - 2, i + 2 and i + 3, if N-cap is i). The N-cap conformation is stabilized by a hydrogen bond between the backbone amide group in the second position of the α-helix and the carbonyl group in the first position of the ß-strand. The occurrence of similar N-capping motifs in different types of ßαß-units was compared and their structural differences caused by the influence of the environment were described. Study results may be useful for protein design and ab initio prediction of the 3D protein structure.

3ß-Corner Stability by Comparative Molecular Dynamics Simulations.

This study explored the mechanisms by which the stability of super-secondary structures of the 3ß-corner type autonomously outside the protein globule are maintained in an aqueous environment. A molecular dynamic (MD) study determined the behavioral diversity of a large set of non-homologous 3ß-corner structures of various origins. We focused on geometric parameters such as change in gyration radius, solvent-accessible area, major conformer lifetime and torsion angles, and the number of hydrogen bonds. Ultimately, a set of 3ß-corners from 330 structures was characterized by a root mean square deviation (RMSD) of less than 5 Å, a change in the gyration radius of no more than 5%, and the preservation of amino acid residues positioned within the allowed regions on the Ramachandran map. The studied structures retained their topologies throughout the MD experiments. Thus, the 3ß-corner structure was found to be rather stable per se in a water environment, i.e., without the rest of a protein molecule, and can act as the nucleus or "ready-made" building block in protein folding. The 3ß-corner can also be considered as an independent object for study in field of structural biology.

Structural features of split and unsplit ßαß-units.

In this study, 1064 nonhomologous "unsplit", "one-strand split" and "two-strand split" right-handed ßαß-units having standard α-helices and loops up to seven residues in length have been analyzed. It was found that the α-helices in these kinds of ßαß-units have different distributions of the hydrophobic and hydrophilic amino acid residues along the chain. In the unsplit ßαß-units, most α-helices have hydrophobic residues in positions N4-N7-N8-N11 or N6-N7-N10, where N1 is the first N-terminal residue. In the one-strand split ßαß-units, most α-helices have hydrophobic residues in positions N4-N7-N8-N11 and those in two-strand split ßαß-units in positions N4-N5-N8-N12. On the other hand, in all kinds of ßαß-units, there are commonly occurring hydrophobic stripes of type C4-C7-C8 at the C-terminal parts of the α-helices. As a rule, the C- and N-terminal hydrophobic stripes overlap and the extent of their overlapping determine the length of α-helices.

PCBOST: Protein classification based on structural trees.

In this paper, we present the protein classification based on structural trees (PCBOST). This is a novel hierarchical classification of proteins that is primarily based on similarity of overall folds of proteins as well as on the modeled folding pathways of proteins. Amino acid sequences, functions of proteins and their evolutionary relationship are not taken into account in this classification. To date the database includes 3847 proteins and domains grouped into six categories having structural similarity and forming six structural trees (total 10,547 PDB-entries). The work on extension of the database and construction of novel structural trees is in progress. The service is free for all users and available at the URL .

Left-handed ßαß-units: frequency of occurrence and arrangement in protein structure.

Communicated by Ramaswamy H. Sarma.

Novel approach for structural identification of protein family: glyoxalase I.

Glyoxalase is one of two enzymes of the glyoxalase detoxification system against methylglyoxal and other aldehydes, the metabolites derived from glycolysis. The glyoxalase system is found almost in all living organisms: bacteria, protozoa, plants, and animals, including humans, and is related to the class of 'life essential proteins'. The enzyme belongs to the expanded Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily. At present the GenBank contains about 700 of amino acid sequences of this enzyme type, and the Protein Data Bank includes dozens of spatial structures. We have offered a novel approach for structural identification of glyoxalase I protein family, which is based on the selecting of basic representative proteins with known structures. On this basis, six new subfamilies of these enzymes have been derived. Most populated subfamilies A1 and A2 were based on representative human Homo sapiens and bacterial Escherichia coli enzymes. We have found that the principle feature, which defines the subfamilies' structural differences, is conditioned by arrangement of N- and C-domains inside the protein monomer. Finely, we have deduced the structural classification for the glyoxalase I and assigned about 460 protein sequences distributed among six new subfamilies. Structural similarities and specific differences of all the subfamilies have been presented. This approach can be used for structural identification of thousands of the so-called hypothetical proteins with the known PDB structures allowing to identify many of already existing atomic coordinate entrees.