Stereoselective aminoacylation of a dinucleoside monophosphate by the imidazolides ofDl-alanine and N-(tert-butoxycarbonyl)-Dl-alanine

Profy, Albert T.; Usher, D. A.

doi:10.1007/bf02257375

Cited by 40 publications

(24 citation statements)

References 68 publications

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“…1). The feasibility of esterification at the internal 2Ј hydroxyl is demonstrated by previous work showing that reaction of dinucleotides with activated amino acids gives acylation at the internal 2Ј and terminal 2Ј(3Ј) positions in ratios ranging from 1:9 to 6:4, depending on the dinucleotide and the buffer concentration (38)(39)(40). The esterification reaction need not be specific, because reactions between an ␣-keto acid and a dinucleotide that cannot catalyze the first step in a synthetic pathway will simply lead to dead-end products.…”

Section: A Model For Catalysis Of Amino Acid Synthesis By Dinucleotidesmentioning

confidence: 99%

A mechanism for the association of amino acids with their codons and the origin of the genetic code

Copley

Smith

Morowitz

2005

Proc. Natl. Acad. Sci. U.S.A.

119

110

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The genetic code has certain regularities that have resisted mechanistic interpretation. These include strong correlations between the first base of codons and the precursor from which the encoded amino acid is synthesized and between the second base of codons and the hydrophobicity of the encoded amino acid. These regularities are even more striking in a projection of the modern code onto a simpler code consisting of doublet codons encoding a set of simple amino acids. These regularities can be explained if, before the emergence of macromolecules, simple amino acids were synthesized in covalent complexes of dinucleotides with ␣-keto acids originating from the reductive tricarboxylic acid cycle or reductive acetate pathway. The bases and phosphates of the dinucleotide are proposed to have enhanced the rates of synthetic reactions leading to amino acids in a small-molecule reaction network that preceded the RNA translation apparatus but created an association between amino acids and the first two bases of their codons that was retained when translation emerged later in evolution.catalysis ͉ origin of life T he genetic code has many regularities (1), of which only a subset have explanations in terms of tRNA function (2) or robustness against deleterious effects of mutation (3, 4) or errors in translation (3, 5). There is a strong correlation between the first bases of codons and the biosynthetic pathways of the amino acids they encode (1, 6). Codons beginning with C, A, and U encode amino acids synthesized from ␣-ketoglutarate (␣-KG), oxaloacetate (OAA), and pyruvate, respectively. ¶ These correlations are especially striking in light of the structural diversity of amino acids whose codons share a first base. For example, codons for Glu and Pro both begin with C, and those for Cys and Leu begin with U. Codons beginning with G encode amino acids that can be formed by direct reductive amination of a simple ␣-keto acid. These include glycine, alanine, aspartate, and glutamate, which can be formed by reductive amination of glyoxalate, pyruvate, OAA, and ␣-KG, respectively. There is also a long-recognized relationship between the hydrophobicity of the amino acid and the second base of its codon (1). Codons having U as the second base are associated with the most hydrophobic amino acids, and those having A as the second base are associated with the most hydrophilic amino acids.We suggest that both correlations can be explained if, before the emergence of macromolecules, simple amino acids were synthesized from ␣-keto acid precursors covalently attached to dinucleotides that catalyzed the reactions required to synthesize specific amino acids (see Fig. 1). This is a significant departure from previous theories attempting to explain the regularities in the genetic code (3). The ''stereochemical'' hypothesis suggests that binding interactions between amino acids and their codons or anticodons dictated the structure of the genetic code (7-10). The ''coevolution'' hypothesis (6) suggests that the original genetic code specifi...

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Section: A Model For Catalysis Of Amino Acid Synthesis By Dinucleotidesmentioning

confidence: 99%

A mechanism for the association of amino acids with their codons and the origin of the genetic code

Copley

Smith

Morowitz

2005

Proc. Natl. Acad. Sci. U.S.A.

119

110

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“…Stereoselective reactions, which could have served as bases for the origin and evolution of the protein-synthesizing system, would seem more fruitful subjects of study. In that vein Profy and Usher (4,5) have shown some stereoselectivity for the L isomer in esterification reactions with amino acids and oligo-or polynucleotides. They also have discussed in some detail the fact that amino acids esterified to ribonucleotides constantly migrate between the 2' and 3' positions ofthe ribose and have emphasized the possible significance of studies on the differential distribution of D and L amino acids between the 2' and 3' positions.…”

mentioning

confidence: 99%

Differential distribution of D and L amino acids between the 2' and 3' positions of the AMP residue at the 3' terminus of transfer ribonucleic acid.

Lacey

Hawkins

Thomas

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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Amino acids esterified to the ribose group of 5'-adenylic acid (AMP) constantly migrate between the 2' and 3' positions of the ribose at a rate of several times per second, which is slower than the rate of peptide-bond synthesis (15-20 per sec). Because the contemporary protein-synthesizing system only incorporates amino acids into protein when they are at the 3' position of the AMP at the terminus of tRNA, the value of the equilibrium constant relative to the 2' and 3' positions is of considerable interest. Differences between D and L isomers in this regard might be especially revealing. We have used N-acetylaminoacyl esters of AMP as models for the 3' terminus oftRNA and find that glycine and the L amino acids consistently distribute predominantly to the 3' position (=67% 3', o33% 2'), but D amino acids distribute to that position generally to a lesser extent and in a manner inversely related to the hydrophobicity of the amino acid side chain. This consistency of the L amino acid preference for the 3' position, combined with the inconsistency of the D amino acid preference, may be one reason for the origin of our contemporary protein-synthesizing system, which forms the peptide bond preferentially with L amino acids and only when they are in the 3' position of the fibose moiety of the AMP residue at the 3' terminus of every tRNA.For all practical purposes, in vivo template-directed protein synthesis proceeds with the incorporation of only L amino acids. This is true in spite of the fact that there are a number of reports that D amino acids can participate in essentially all of the reactions involved, including peptide-bond synthesis (1-3). The preference for L appears to be due to preferences at each of several steps, resulting in a cumulative preference for the L isomer of 4 orders of magnitude. A basic question remains, though, as to why these enzymatic preferences for the L amino acids have evolved. In fact, it has been difficult to show how abiological reactions could result in preferential synthesis or degradation of one isomer. Stereoselective reactions, which could have served as bases for the origin and evolution of the protein-synthesizing system, would seem more fruitful subjects of study. In that vein Profy and Usher (4, 5) have shown some stereoselectivity for the L isomer in esterification reactions with amino acids and oligo-or polynucleotides. They also have discussed in some detail the fact that amino acids esterified to ribonucleotides constantly migrate between the 2' and 3' positions ofthe ribose and have emphasized the possible significance of studies on the differential distribution of D and L amino acids between the 2' and 3' positions. The interest is in the fact that amino acids esterified to the AMP residue at the 3' terminus of the tRNA are constantly migrating back and forth several times a second (6), and the amino acid is only incorporated into protein when it is in the 3' position (7-10). Furthermore, it was established by Taiji et al. (6) that the rate of amino acid trans...

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“…A handful of investigators have previously demonstrated preferred binding of various L-amino acids to their D-(anti)codons (30)(31)(32)(33) The current hypothesis makes the unique, and currently untested, prediction that D-amino acids should have equal affinity for the directionally inverse L-(anti)codons. Thus, if L-methionine prefers D-AUG, D-methionine will prefer L-GUA, not L-AUG (see section on Stereochemistry, directionality and affinity, above).…”

Section: Experimental Testsmentioning

confidence: 89%

“…(3) Some amino acids bind to some polynucleotide sequences with higher affinity than other possible pairings. (10)(11)(12)(13)(14)(15)(16)(17)(30)(31)(32) . Since binding of compounds buffers each compound structurally and chemically from reactions and degradation processes, the higher the affinity a pair of compounds had, the greater the likelihood that their complex, or the components of their complex, would survive to participate in the formation of the genetic code.…”

Section: Stereochemistry Directionality and Affinitymentioning

confidence: 99%

Simultaneous origin of homochirality, the genetic code and its directionality

Root‐Bernstein

2007

BioEssays

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The origin of homochirality in molecules characterizing living systems has remained a mystery since Pasteur's recognition of the problem some 150 years ago.(2-5) Most theories also assume that homochirality emerged in one class of molecules (e.g. ribose) from which it was enriched in other molecules (e.g. amino acids) as well.(2-5)I propose a novel, experimentally testable hypothesis describing a process by which selective chirality in amino acids and ribonucleotides emerged simultaneously and hand-in-hand with the origin and directionality of the genetic code within a system of interactions involving amino acids, peptides, nucleotide bases, their sugars and polynucleotides.

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Stereoselective aminoacylation of a dinucleoside monophosphate by the imidazolides ofDl-alanine and N-(tert-butoxycarbonyl)-Dl-alanine

Cited by 40 publications

References 68 publications

A mechanism for the association of amino acids with their codons and the origin of the genetic code

A mechanism for the association of amino acids with their codons and the origin of the genetic code

Differential distribution of D and L amino acids between the 2' and 3' positions of the AMP residue at the 3' terminus of transfer ribonucleic acid.

Simultaneous origin of homochirality, the genetic code and its directionality

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