Stereospecificity in Enzymology: Its Place in Evolution

Benner, Steven A.; Glasfeld, Arthur; Piccirilli, Joseph A.

doi:10.1002/9780470147283.ch3

Cited by 22 publications

(2 citation statements)

References 150 publications

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“…Given this evolutionary diversity, there is no reason that the behavior of a specific DNA polymerase could be extrapolated to the behavior of all polymerase. This is not true for many features of stereochemistry in other classes of enzymes (36). …”

Section: Discussionmentioning

confidence: 99%

Nucleoside alpha-thiotriphosphates, polymerases and the exonuclease III analysis of oligonucleotides containing phosphorothioate linkages

Yang¹,

Sismour²,

Benner³

2007

Nucleic Acids Research

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The use of DNA polymerases to incorporate phosphorothioate linkages into DNA, and the use of exonuclease III to determine where those linkages have been incorporated, are re-examined in this work. The results presented here show that exonuclease III degrades single-stranded DNA as a substrate and digests through phosphorothioate linkages having one absolute stereochemistry, assigned (assuming inversion in the polymerase reaction) as S, but not the other absolute stereochemistry. This contrasts with a general view in the literature that exonuclease III favors double-stranded nucleic acid as a substrate and stops completely at phosphorothioate linkages. Furthermore, not all DNA polymerases appear to accept exclusively the (R) stereoisomer of nucleoside alpha-thiotriphosphates [and not the (S) diastereomer], a conclusion inferred two decades ago by examination of five Family-A polymerases and a reverse transcriptase. This suggests that caution is appropriate when extrapolating the detailed behavior of one polymerase from the behaviors of other polymerases. Furthermore, these results provide constraints on how exonuclease III–thiotriphosphate–polymerase combinations can be used to analyze the behavior of the components of a synthetic biology.

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Section: Discussionmentioning

confidence: 99%

Nucleoside alpha-thiotriphosphates, polymerases and the exonuclease III analysis of oligonucleotides containing phosphorothioate linkages

Yang¹,

Sismour²,

Benner³

2007

Nucleic Acids Research

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“…The choices made by triosephosphate and by aconitase are well known to be chiral choices between enantiotopic atoms or groups of atoms. The critical point here is that there are a multitude of enzyme catalyzed reactions distinguishing enantiotopic groups in which the product of the reaction would be identical whichever of the enantiotopic groups were chosen (Arigoni and Eliel 1969;Benner et al 1989;Cornforth 1974). Therefore, why should an enzyme bother to make the distinction?…”

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confidence: 99%

Homochirality in Life: Two Equal Runners, One Tripped

Green

Jain

2009

Orig Life Evol Biosph

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Strong arguments can be found in the literature addressed to the question of the origin of homochirality in life, supporting the hypothesis that primordial life could have evolved in both homochiral forms and that early on when life was still rarely found, random events led to the survival of only one of these living mirror images. This proposal is an alternative to the generally accepted view that small enantiomeric excesses of biologically important molecules were amplified to homochirality prior to life's origin. Acceptance of the possibility of "two equal runners" leads to the importance of research investigations on routes to formation of ensembles of racemic mixtures of isotactic biologically interesting polymers, supramolecular entities and aggregates.

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Organic Stereochemistry. Part 7

Testa

2013

Helvetica Chimica Acta

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This review continues a general presentation of the principles of stereochemistry with special emphasis on the biomedicinal sciences. Here, we discuss and illustrate the phenomenon of substrate stereoselectivity in biochemistry (endogenous metabolism) and principally in xenobiochemistry or drug metabolism. The review begins with an overview of the stereoselective processes occurring in the biomedicinal sciences. The general rule is for distinct stereoisomers, be they enantiomers or diastereoisomers, to elicit different pharmacological responses (Part 5), to a lesser extent be transported with different efficacies (Part 5), and to be metabolized at different rates (this Part). In other words, biological environments discriminate between stereoisomers both when acting on them and when being acted upon by them. The concept of substrate stereoselectivity describes this phenomenon in endogenous biochemistry and xenobiotic metabolism, as discussed and illustrated in the present Part. The sister concept of product stereoselectivity will be presented in Part 8.

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Stereospecificity in Enzymology: Its Place in Evolution

Cited by 22 publications

References 150 publications

Nucleoside alpha-thiotriphosphates, polymerases and the exonuclease III analysis of oligonucleotides containing phosphorothioate linkages

Nucleoside alpha-thiotriphosphates, polymerases and the exonuclease III analysis of oligonucleotides containing phosphorothioate linkages

Homochirality in Life: Two Equal Runners, One Tripped

Organic Stereochemistry. Part 7

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