Terry L. Marsh

Bio: Terry L. Marsh is an academic researcher from Indiana University. The author has contributed to research in topics: RNase P & RNA. The author has an hindex of 3, co-authored 4 publications receiving 2573 citations. Previous affiliations of Terry L. Marsh include University of Colorado Boulder.

RNA catalysis and the origin of life.

Abstract: Until the discovery of catalytic RNAs, first the self-splicing intron in Tetrahymena and then the bacterial RNAse P, cellular enzymes had always seemed to be protein in nature. The recognition that RNA can catalytically make and break phosphodiester bonds simplifies some of the assumptions required of a rudimentary self-replicating entity. Available information on the chemistry of RNA-catalyzed reactions is reviewed, with particular attention to self-splicing introns and tRNA processing by RNase P. An explicit model for a self-replicating RNA is described. The model postulates a nucleotide binding/polymerization site in the RNA, and takes advantage of intrinsic fluidity in RNA higher order structure to dissociate parent and progeny complementary strands.

Ribonuclease P catalysis differs from ribosomal RNA self-splicing

Abstract: Two RNA-catalyzed reactions have been described, the Tetrahymena self-splicing ribosomal RNA and ribonuclease P. The Tetrahymena self-splicing reaction proceeds through a transesterification cascade that is dependent upon nucleophilic attacks by ribose 3'-OH groups. Periodate oxidation of the catalytic (or substrate) RNA, which destroys the nucleophilicity of RNA 3' termini, did not inhibit ribonuclease P activity. Thus, catalysis by ribonuclease P differs from the self-splicing reaction.

Aromatic-aromatic interaction: a mechanism of protein structure stabilization

Abstract: Analysis of neighboring aromatic groups in four biphenyl peptides or peptide analogs and 34 proteins reveals a specific aromatic-aromatic interaction. Aromatic pairs (less than 7 A between phenyl ring centroids) were analyzed for the frequency of pair type, their interaction geometry (separation and dihedral angle), their nonbonded interaction energy, the secondary structural locations of interacting residues, their environment, and their conservation in related molecules. The results indicate that on average about 60 percent of aromatic side chains in proteins are involved in aromatic pairs, 80 percent of which form networks of three or more interacting aromatic side chains. Phenyl ring centroids are separated by a preferential distance of between 4.5 and 7 A, and dihedral angles approaching 90 degrees are most common. Nonbonded potential energy calculations indicate that a typical aromatic-aromatic interaction has energy of between -1 and -2 kilocalories per mole. The free energy contribution of the interaction depends on the environment of the aromatic pair. Buried or partially buried pairs constitute 80 percent of the surveyed sample and contribute a free energy of between -0.6 and -1.3 kilocalories per mole to the stability of the protein's structure at physiologic temperature. Of the proteins surveyed, 80 percent of these energetically favorable interactions stabilize tertiary structure, and 20 percent stabilize quaternary structure. Conservation of the interaction in related molecules is particularly striking.

Origin of life: The RNA world

Abstract: Sur la base de la decouverte d'activites enzymatiques de certains ARN (chez E. coli au cours de la maturation des ARN+ et chez Tetrahymena avec un exon d'un ARNr a auto-epissage), l'auteur postule un systeme, auto-replicatif a l'origine uniquement compose de molecules d'ARN

The Structural Basis of Ribosome Activity in Peptide Bond Synthesis

Abstract: Using the atomic structures of the large ribosomal subunit from Haloarcula marismortui and its complexes with two substrate analogs, we establish that the ribosome is a ribozyme and address the catalytic properties of its all-RNA active site. Both substrate analogs are contacted exclusively by conserved ribosomal RNA (rRNA) residues from domain V of 23S rRNA; there are no protein side-chain atoms closer than about 18 angstroms to the peptide bond being synthesized. The mechanism of peptide bond synthesis appears to resemble the reverse of the acylation step in serine proteases, with the base of A2486 (A2451 in Escherichia coli) playing the same general base role as histidine-57 in chymotrypsin. The unusual pK(a) (where K(a) is the acid dissociation constant) required for A2486 to perform this function may derive in part from its hydrogen bonding to G2482 (G2447 in E. coli), which also interacts with a buried phosphate that could stabilize unusual tautomers of these two bases. The polypeptide exit tunnel is largely formed by RNA but has significant contributions from proteins L4, L22, and L39e, and its exit is encircled by proteins L19, L22, L23, L24, L29, and L31e.