Biomedical subjects

J Seetharaman

Publications and source records attributed to J Seetharaman.

7 recordsLinked to original sources

PubMed1998

X-ray crystal structure of the human galectin-3 carbohydrate recognition domain at 2.1-A resolution.

Galectins are a family of lectins which share similar carbohydrate recognition domains (CRDs) and affinity for small beta-galactosides, but which show significant differences in binding specificity for more complex glycoconjugates. We report here the x-ray crystal structure of the human galectin-3 CRD, in complex with lactose and N-acetyllactosamine, at 2.1-A resolution. This structure represents the first example of a CRD determined from a galectin which does not show the canonical 2-fold symmetric dimer organization. Comparison with the published structures of galectins-1 and -2 provides an explanation for the differences in carbohydrate-binding specificity shown by galectin-3, and for the fact that it fails to form dimers by analogous CRD-CRD interactions.

Animals↗

PubMed1998

Identification of the ice-binding surface on a type III antifreeze protein with a "flatness function" algorithm.

Antifreeze proteins (AFPs) adsorb to surfaces of growing ice crystals, thereby arresting their growth. The prevailing hypothesis explains the nature of adsorption in terms of a match between the hydrophilic side chains on the AFP's ice-binding surface (IBS) and the water molecules on the ice surface. The number and spatial arrangement of hydrogen bonds thus formed have been proposed to account, respectively, for the binding affinity and specificity. The crystal structure of a type III AFP from ocean pout (isoform HPLC-3) has been determined to 2.0-A resolution. The structure reveals an internal dyad motif formed by two 19-residue, loop-shaped elements. Based on of the flatness observed on the type I alpha-helical AFP's IBS, an automated algorithm was developed to analyze the surface planarity of the globular type III AFP and was used to identify the IBS on this protein. The surface with the highest flatness score is formed by one loop of the dyad motif and is identical to the IBS deduced from earlier mutagenesis studies. Interestingly, 67% of this surface contains nonpolar solvent-accessible surface area. The success of our approach to identifying the IBS on an AFP, without considering the presence of polar side chains, indicates that flatness is the first approximation of an IBS. We further propose that the specificity of interactions between an IBS and a particular ice-crystallographic plane arises from surface complementarity.

Algorithms↗

PubMed1997

Gem-dialkyl succinic acids: a novel class of inhibitors for carboxypeptidases.

gem-Dimethylsuccinic acid and its higher homolog, 2-methyl-2-ethylsuccinic acid (MESA) are highly potent inhibitors of both carboxypeptidase A (CPA) and B. The inhibition constant of MESA for CPA (0.11 microM for the racemic mixture) is remarkable considering the relatively simple structure of the compound. The molecular feature which is crucial for high affinity binding to both carboxypeptidases appears to be the nonpolar gem-dialkyl locus. The structure of the complex between MESA and CPA has been determined by X-ray crystallography to 2.0 A resolution and shows the R enantiomer of the inhibitor to be bound in a generally substrate-like manner. The carboxymethyl group is coordinated to the Zn ion in the active site, and the gem-dialkyl locus corresponds in position to the alpha-carbon of the C-terminal amino acid in a peptide substrate. The methyl group of the inhibitor occupies a cavity in the enzyme which is apparently not filled upon substrate-binding. We postulate that this cavity (the alpha-methyl hole) is designed to allow the proximal Glu-270 residue to undergo a critical movement during catalysis. The hydrophobic nature of the above cavity may play a role in modulating the reactivity of this residue. These results suggest that similar cenophilic(empty-loving) inhibitors may be found for other enzymes.

Animals↗

PubMed1996

Pattern recognition approach to nucleic acid sequences.

A pattern recognition method through the two dimensional matrix representation of the nucleic acids sequence is developed. This approach of two dimensional plotting primarily enables to visualize all types of bonding between different bases in a RNA or DNA. The two dimensional matrix uses the capability of intramolecular Watson-Crick type (A-U and C-G) and Wobble type (G-U) base pairing. The method discusses both parallel and anti-parallel stranded base pairing. The application of the method to tRNA is shown.

Base Composition↗

PubMed1996

A new simple method of representing relative orientation of bases in DNA helical structures.

It is shown that the strandwise correlation of the torsion angles in Nucleic acid structures can throw light on the aspects like helical distortion, in double helical and other associated forms. The single crystal X-ray coordinates for 7 A-DNA, 29 B-DNA, 8 Z-DNA and 4 tRNA structures are used to calculate the glycosyl angle chi and they are plotted in a two dimensional plot. A new torsion angle pi is defined as O4'-C1'-N1(9)-X, where X is a fictitious atom on the normal at N1(9). The chi 1 vs. chi 2 plots (where 1 and 2 refer to I and II-strand of DNA respectively) show the characteristic clustering features of A, B and Z DNAs. They are also compactly reflected in the modified graphical representation like (chi 1 + chi 2) vs. magnitude of chi 1 - chi 2 plot. chi 1 vs. chi 2 plot of the Hoogsteen type of base pairing obtained from the tRNA structures is off diagonal. The distortions due to complexing of the structures under each category, in particular, B-DNAs is readily observed. The observed points of A/B hybrid form clusters between A and B uncomplexed forms. The new torsion angle pi shows similar behavior as that of chi.

Base Composition↗

PubMed1995

Analysis of codon usage: positional preference in various organisms.

The degree of preference of the four nucleotides C, G, A and U in the three positions I, II and III of the codons of 15137 genes of various individual organisms is examined using the nucleotide sequence data obtained from the GenBank Genetic Sequence Data Bank (Release 65.0, Sep., 1990). It is found that G, A and C, are preferred maximally in the three positions respectively. Similarly, U, G and A are preferred minimally in these positions. The analysis shows a correlation in the positional base preference which discriminates against codons with the same base in all three positions or in the adjacent positions.

Animals↗

PubMed1993

A unique or essentially unique single parametric characterisation of biopolymeric structures.

A generalised method of characterising the three dimensional structure of any biopolymer is proposed. The method makes use of rotation and superposition of identical rigid monomeric units that comprise the polymer. Out of the various parameters involved (refers the seven parametric representation of relating two identical rigid bodies in space), the angle of rotation and superposition termed as 'phi s' turns out to be essentially unique. An ideal biopolymer with n identical rigid units is characterised by (n-1) such unique angles. In applying the results to real biopolymers, the importance of recognising that monomeric units are no more rigid but only quasi-rigid is emphasised. However, by appropriate choice of 'rigid' fraction of the quasi-rigid monomers, one is led, as first approximation, to essentially unique characterisation of the biopolymer with (n-1) such unique angles. The phi s as a function of residue number acts essentially as a finger print of the given polymeric fold and the conformation of the chosen biopolymer. However, the full set of seven parameters are needed for model building. It is emphasised that the method is general in its application to any polymer and the application of the results to proteins and nucleic acids is illustrated.

Amino Acids↗