Biomedical subjects

Lipika Pal

Publications and source records attributed to Lipika Pal.

4 recordsLinked to original sources

PubMed2005

3(10)-Helix adjoining alpha-helix and beta-strand: sequence and structural features and their conservation.

Does the amino acid use at the terminal positions of an alpha-helix become altered depending on the context-more specifically, when there is an adjoining 3(10)-helix, and can a single helical cylinder encompass the resultant composite helix? An analysis of 138 and 107 cases of 3(10)-alpha and alpha-3(10) composite helices, respectively, found in known protein structures indicate that the secondary structural element occurring first imposes its characteristics on the sequence of the structural element coming next. Thus, when preceded by a 3(10)-helix, the preference of proline to occur at the N1 position of an alpha-helix is shifted to the N2 position, a typical characteristic of the C-terminal capping of the 3(10)-helix. When an alpha- or a 3(10)-helix leads into a helix of the other type, there is a bend at the junction, especially for the 3(10)-alpha composite, with the two junction residues facing inward and buried within the structure. Thus a single helical cylinder may not properly represent a composite helix, the bend providing a means for the tertiary structure to assume a globular shape, very much akin to what a proline-induced kink does to an alpha-helix. The tertiary structural context in which beta-3(10) and 3(10)-beta composites occurs can be different, causing the angle between the secondary structural elements in the two cases to be different. Composites of 3(10)-helices and beta-strands are much more conserved among members in families of homologous structures than those between two types of helices; in many of the former instances, the 3(10)-helix constitutes the loops in beta-hairpin or beta-beta-corner motifs. The overall fold of the chain may be more conserved than the actual identify of the secondary structure elements in a composite.

Amino Acid Sequence↗

PubMed2004

Expanded turn conformations: characterization and sequence-structure correspondence in alpha-turns with implications in helix folding.

Like the beta-turns, which are characterized by a limiting distance between residues two positions apart (i, i+3), a distance criterion (involving residues at positions i and i+4) is used here to identify alpha-turns from a database of known protein structures. At least 15 classes of alpha-turns have been enumerated based on the location in the phi,psi space of the three central residues (i+1 to i+3)-one of the major being the class AAA, where the residues occupy the conventional helical backbone torsion angles. However, moving towards the C-terminal end of the turn, there is a shift in the phi,psi angles towards more negative phi, such that the electrostatic repulsion between two consecutive carbonyl oxygen atoms is reduced. Except for the last position (i+4), there is not much similarity in residue composition at different positions of hydrogen and non-hydrogen bonded AAA turns. The presence or absence of Pro at i+1 position of alpha- and beta-turns has a bearing on whether the turn is hydrogen-bonded or without a hydrogen bond. In the tertiary structure, alpha-turns are more likely to be found in beta-hairpin loops. The residue composition at the beginning of the hydrogen bonded AAA alpha-turn has similarity with type I beta-turn and N-terminal positions of helices, but the last position matches with the C-terminal capping position of helices, suggesting that the existence of a "helix cap signal" at i+4 position prevents alpha-turns from growing into helices. Our results also provide new insights into alpha-helix nucleation and folding.

Amino Acid Sequence↗

PubMed2003

Sequence and structure patterns in proteins from an analysis of the shortest helices: implications for helix nucleation.

The shortest helices (three-length 3(10) and four-length alpha), most abundant among helices of different lengths, have been analyzed from a database of protein structures. A characteristic feature of three-length 3(10)-helices is the shifted backbone conformation for the C-terminal residue (phi,psi angles: -95 degrees,0 degrees ), compared to the rest of the helix (-62 degrees,-24 degrees ). The deviation can be attributed to the release of electrostatic repulsion between the carbonyl oxygen atoms at the two C-terminal residues and further stabilization (due to a more linear geometry) of an intrahelical hydrogen bond. A consequence of this non-canonical C-terminal backbone conformation can be a potential origin of helix kinks when a 3(10)-helix is sequence-contiguous at the alpha-helix N-terminal. An analysis of hydrogen bonding, as well as hydrophobic interactions in the shortest helices shows that capping interactions, some of them not observed for longer helices, dominate at the N termini. Further, consideration of the distribution of amino acid residues indicates that the shortest helices resemble the N-terminal end of alpha-helices rather than the C terminus, implying that the folding of helices may be initiated at the N-terminal end, which does not get propagated in the case of the shortest helices. Finally, pairwise comparison of beta-turns and the shortest helices, based on correlation matrices of site-specific amino acid composition, and the relative abundance of these short secondary structural elements, leads to a helix nucleation scheme that considers the formation of an isolated beta-turn (and not an alpha-turn) as the helix nucleation step, with shortest 3(10)-helices as intermediates between the shortest alpha-helix and the beta-turn. Our results ascribe an important role played by shortest 3(10)-helices in proteins with important structural and folding implications.

Amino Acid Motifs↗

PubMed2002

Variants of 3(10)-helices in proteins.

An analysis of the shortest 3(10)-helices, containing three helical residues and two flanking capping residues that participate in two consecutive i + 3 --> i hydrogen bonds, shows that not all helices belong to the classic 3(10)-helix, where the three central residues adopt the right-handed helical conformation (alpha(R)). Three variants identified are: 3L10-helix with all residues in the left-handed helical region (alpha(L)), 3EL10-helix where the first residue is in the extended region followed by two residues in the alpha(L) conformation, and its mirror-image, the 3E'R10-helix. In the context of these helices, as well as the equivalent variants of alpha-helices, the length dependence of the handedness of secondary structures in protein structure is discussed. There are considerable differences in the amino acid preferences at different positions in the various types of 3(10)-helices. Each type of 3(10)-helix can be thought to be made up of an extension of a particular type of beta-turn (made up of residues i to i + 3) such that the (i + 3)th residue assumes the same conformation as the preceding residue. Distinct residue preferences at i and i + 3 positions seem to decide whether a particular stretch of four residues will be a beta-turn or a 3(10)-helix in the folded structure.

Amino Acid Motifs↗