Biomedical subjects

Y C Sekharudu

Publications and source records attributed to Y C Sekharudu.

5 recordsLinked to original sources

PubMed1989

Water-inserted alpha-helical segments implicate reverse turns as folding intermediates.

Information relevant to the folding and unfolding of alpha helices has been extracted from an analysis of protein structures. The alpha helices in protein crystal structures have been found to be hydrated, either externally by a water molecule hydrogen bonding to the backbone carbonyl oxygen atom, or internally by inserting into the helix hydrogen bond and forming a hydrogen-bonded bridge between the backbone carbonyl oxygen and the amide nitrogen atoms. The water-inserted alpha-helical segments display a variety of reverse-turn conformations, such as type III, type II, type I, and opened out, that can be considered as folding intermediates that are trapped in the folding-unfolding process of alpha helices. Since the alpha helix, most turns, and the extended beta strand occupy contiguous regions in the conformational space of phi, psi dihedral angles, a plausible pathway can be proposed for the folding-unfolding process of alpha helices in aqueous solution.

Hydrogen Bonding↗

PubMed1988

A structure-function relationship for the calcium affinities of regulatory proteins containing 'EF-hand' pairs.

Using a series of homologous calcium-binding proteins, a quantitative structure-activity relationship (QSAR), log(1/Kd) = -18.986 - 1.6278(X1) + 0.7981(X2) + 0.2312(X3), has been established, which relates the calcium-binding affinities (1/Kd) of the regulatory proteins with (i) the net ligand charge (X1) of the two calcium binding loops, (ii) the hydrophobicity (X2) of the beta-sheet segment of the loops and (iii) the hydrophobicity (X3) of the four 'EF-hand' helices. It is found that the binding affinities are influenced by the 'EF-hand' pair rather than the individual 'EF-hands'. The QSAR, in addition to explaining satisfactorily the large variation in the observed calcium affinities, can predict the affinities of the 'EF-hand' pairs in other proteins from the amino acid sequence and can also account for the changes in the affinities caused by substitution in the hydrophobic and/or metal-coordinating residues. Thus, this relationship can be employed in protein design and engineering. The method is potentially useful in the development of similar relationships for the binding of other proteins to substrates, inhibitors, drugs and co-factors.

Amino Acid Sequence↗

PubMed1987

The conformation of glycans of the oligo-D-mannosidic type, and their interaction with concanavalin A: a computer-modelling study.

The favored conformations of glycans of the oligo-D-mannosidic type have been determined by using empirical energy calculations. An interesting aspect is that the alpha-(1----3)-linked terminal D-mannose residue of the outer trimannosidic core fragment, in all the conformations which fall within 5 kcal.mol-1 of the global minimum, always lies close to the chitobiose core. These models are in general agreement with the available n.m.r. data. The probable modes of binding of these glycans to concanavalin A (Con A) were determined, by using a computer-modelling technique which identifies the positions for the different conformers of the carbohydrate in the binding site of Con A, based on stereochemical considerations. These studies showed that Con A can bind only to two of the three terminal D-mannose residues in these glycans, because the D-mannose residue which lies close to the chitobiose core is inaccessible for the binding of Con A. Of these two terminal D-mannose residues, the alpha-(1----6)-linked D-mannose may bind the more strongly. Furthermore, it is shown that the internal D-mannose residue will, at best, interact very weakly with the carbohydrate-binding site of Con A. These results rationalize well the available data on the binding affinity of these glycans to Con A. They further support the conclusion that the binding affinity of a glycan to Con A does not depend on the number in the glycan, of D-mannose residues which possess free 3-, 4-, and 6-hydroxyl groups, but, rather, on the accessibility of these residues to Con A.

Carbohydrate Conformation↗

PubMed1987

Ion pairs in alpha helices.

A survey of 47 globular proteins was made to determine the probability of occurrence of ion pairs separated by 1,2,3,... and 8 residues in the alpha helices. As a control, the probability of occurrence of like charged pairs was also determined. The survey showed that ion pairs of the type i,i +/- 3 and i, i +/- 4 are the most predominant. Such a preference was not observed for like charged pairs. The observed frequency of ion pairs is significantly greater than their expected frequency. The normalized frequencies of occurrence of the ion pairs were also found to increase generally with the helix length. These results indicate that the ion pairs may contribute to the stability of solvent-exposed alpha helices. Since the stabilization of protein secondary structure enhances the stability of protein tertiary structure, these results may throw light on the mechanism of protein folding.

Amino Acids↗

PubMed1984

The modes of binding methyl-alpha (and beta)-D-glucopyranosides and some of their derivatives to concanavalin A--a theoretical approach.

The probable modes of binding of Methyl--alpha (and beta)-D-glucopyranosides and some of their derivatives to concanavalin A have been proposed from theoretical studies. Theory predicts that beta-MeGlcP can bind to ConA in three different modes whereas alpha-MeGlcP can bind only in one mode. beta-MeGlcP in its most favourable mode of binding differs from alpha-MeGlcP in its alignment in the active-site of the lectin where it binds in a flipped or inverted orientation. Methyl substitution at the C-2 atom of the alpha-MeGlcP does not significantly affect the possible orientations of the sugar in the active-site of the lectin. Methyl substitution at C-3 or C-4, however, affects the allowed orientations drastically leading to the poor inhibiting power of Methyl-3-O-methyl-alpha-D-glucopyranoside and the inactivity of Methyl-4-O-methyl-alpha-D-glycopyranoside. These studies suggest that the increased activity of the alpha-MeGlcP over beta-MeGlcP may be due to the possibility of formation of better hydrogen bonds and to hydrophobic interactions rather than to steric factors as suggested by earlier workers. These models explain the available NMR and other binding studies.

Binding Sites↗