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Biomedical subjects

M Sundaralingam

Publications and source records attributed to M Sundaralingam.

At least 145 records · Page 8Linked to original sources

Mechanisms of chain folding in nucleic acids. The (omega, omega) plot and its correlation to the nucleotide geometry in yeast tRNAPhe1.

The (omega', omega) polot depicting the internucleotide P-O bond rotation angles in yeast phenylalanyl transfer RNA has established the interdependence of the phosphodiesters and the nucleotide geometries in the folding of the polynucleotide backbone. The plot distinguishes the regions characteristic of secondary helical structures and tertiary structural loops and bends. The folding of the polynucleotide chain is accomplished either solely by rotations around the P-O bonds or in concert with rotations around the nucleotide C4'-C5' bond with or without changes in the sugar ring pucker. In spite of differences in nucleotide sequence and intraloop tertiary interactions in the anticodon and pseudouridine loops, a characteristic repeating structural unit is found for the sugar-phosphate backbone of the tetranucleotide segment around the sharp turns.

Anticodon↗

Structlre of transfer RNA molecules containing the long variable loop.

A structure is proposed for the type II tRNA molecules containing the long variable loop and the tertiary base interactions here are compared with type I tRNAs having the short variable loop. The type II tRNAs are similar to the type I tRNAs in their tertiary base pairing interactions but differ from them generally by not having the tertiary base triples. The long variable loop, which is comprised of a helical stem and a loop at the end of it, emerges from the deep groove side of the dihydrouridine helix, and is tilted roughly 30 degrees to the plane formed by the amino acid-pseudo-uridine and anticodon-dihydrouridine helices found in yeast tRNAPhe. The fact that many of the type I tRNAs also lack the full compliment of base triples suggests that the tertiary base pairs may alone suffice to sustain the tRNA fold required for its biological function. The base triples and the variable loop appear to have little functional significance. The base type at position 9 is correlated with the number of base triples and G-C base pairs in the dihydrouridine stem.

Base Sequence↗

Analysis of the possible helical structures of nucleic acids and polynucleotides. Application of (n-h) plots.

The two helical parameters n and h where n is the number of nucleotide residues per turn and h is the height per nucleotide residue have been evaluated for single stranded helical polynucleotide chains comprising C(3') -endo and C(2') endo class of nucleotides. The helical parameters are found to be especially sensitive to the C(4')-C(3') (sugar pucker) and the C(4')-C(5') torsions. The (n-h) plots display only one important helix forming domain for each class of nucleotides characterized by the sugar pucker and the C(4')-C(5') torsion. A correlation between the (n-h) plots and the known RNA (A,A') and DNA (A,B,C) helical forms has been established. It is found that all forms of helices except the C-DNA possess a favorable combination of P-O torsions. The analysis of the (n-h) plots suggests that C-DNA can have a conformation very similar to B-DNA. Although the (n-h) plots predict the stereochemical possibility of both right-handed and left-handed helices, nucleic acids apparently prefer right-handed conformation because of the energetics associated with the sugar-phosphate backbone and the base.

Binding Sites↗

Atomic coordinates and molecular conformation of yeast phenylalanyl tRNA. An independent investigation.

The atomic coordinates of yeast tRNA(Phe) in the monoclinic crystal form have been determined by an independent analysis from a model built into a 3 A MIR map. The overall molecular structure is found to be in agreement with those reported for the same crystal form by Ladner et al. (1975) and for the orthorhombic form by Quigley et al. (1975) and Kim et al. (1975). However, significant differences between any two of the four models are found in certain local regions of the molecule. The structure is analyzed in terms of the nucleotide stereochemistry and internucleotide phosphodiesters. A striking observation is that the majority of the nucleotide moieties occur in the conformation preferred by the constituent mononucleotides themselves. The internucleotide P-O bonds afford the primary source of flexibility for the folding of the polynucleotide backbone while the sugar pucker and C(4')-C(5') torsions provide the secondary source of flexibility.

Binding Sites↗

Backbone conformations in secondary and tertiary structural units of nucleic acids. Constraint in the phosphodiester conformation.

The possible backbone phosphodiester conformations in a dinucleoside monophosphate and a dinucleoside triphosphate have been investigated by semiempirical energy calculations. Conformational energies have been computed as a function of the rotations omega' and omega about the internucleotide P-O(3') and P-O(5') linkages, with the nucleotide residues themselves assumed to be in one of the preferred [C(3')-endo] conformations. The terminal phosphates in a dinucleoside triphosphate greatly limit the possible conformations for the backbone (in a polynucleotide) compared to a dinucleoside monophosphate. There appear to be two major types of conformations that are favored for the backbone. The phosphodiester conformation (omega',omega) approximately (290 degrees ,290 degrees ) characteristic of helical structures is one of them, indicating that the polynucleotide backbone shows an inherent tendency for the helical conformation. The other favored conformation is centered at (omega',omega) approximately (190 degrees ,300 degrees ) and results in an extended backbone structure with unstacked bases. A third possible conformation centered at (omega', omega) approximately (200 degrees , 60 degrees ) and the (190 degrees , 300 degrees ) conformation appear to be important for the folding of a polynucleotide chain. The conformation (omega',omega) approximately (80 degrees ,80 degrees ), observed in a dinucleoside monophosphate and believed to be a candidate for producing an abrupt turn in a polynucleotide chain, is found to be stereochemically unfavorable in a dinucleoside triphosphate and a polynucleotide.

Models, Molecular↗