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Ribosyl geometry in the transition state of Streptococcus pneumoniae methylthioadenosine nucleosidase from the 3'-(2)H kinetic isotope effect.

ABSTRACT: Synthesis of [3'-2H]-labeled 5'-methylthioadenosine (MTA) derivatives permitted measurement of the [3'-2H] KIE of the reaction catalyzed by Streptococcus pneumoniae methylthioadenosine nucleosidase (spMTAN). The key [3'-2H] KIE revealed the partial 3'-OH polarization and H3'-endo-->exo ribosyl configuration at the spMTAN transition state. A new understanding of the transition state stabilization of spMTAN-catalyzed hydrolysis is uncovered in structural features at the spMTAN transition state.

SUBMITTER: Luo M

PROVIDER: S-EPMC9768846 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Ribosyl geometry in the transition state of Streptococcus pneumoniae methylthioadenosine nucleosidase from the 3'-(2)H kinetic isotope effect.

Luo Minkui M Schramm Vern L VL

Journal of the American Chemical Society 20080812 35

Synthesis of [3'-2H]-labeled 5'-methylthioadenosine (MTA) derivatives permitted measurement of the [3'-2H] KIE of the reaction catalyzed by Streptococcus pneumoniae methylthioadenosine nucleosidase (spMTAN). The key [3'-2H] KIE revealed the partial 3'-OH polarization and H3'-endo-->exo ribosyl configuration at the spMTAN transition state. A new understanding of the transition state stabilization of spMTAN-catalyzed hydrolysis is uncovered in structural features at the spMTAN transition state. ...[more]

PMID: 18693725

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Transition-state analysis of S. pneumoniae 5'-methylthioadenosine nucleosidase.

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Transition-State Analogues of Campylobacter jejuni 5'-Methylthioadenosine Nucleosidase.

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Project description: Not available

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| S-EPMC3268516 | biostudies-literature

Selective Inhibitors of Helicobacter pylori Methylthioadenosine Nucleosidase and Human Methylthioadenosine Phosphorylase.

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| S-EPMC6635953 | biostudies-literature

Kinetic Isotope Effects and Transition State Structure for Human Phenylethanolamine N-Methyltransferase.

Project description:Phenylethanolamine N-methyltransferase (PNMT) catalyzes the S-adenosyl-l-methionine (SAM)-dependent conversion of norepinephrine to epinephrine. Epinephrine has been associated with critical processes in humans including the control of respiration and blood pressure. Additionally, PNMT activity has been suggested to play a role in hypertension and Alzheimer's disease. In the current study, labeled SAM substrates were used to measure primary methyl-14C and 36S and secondary methyl-3H, 5'-3H, and 5'-14C intrinsic kinetic isotope effects for human PNMT. The transition state of human PNMT was modeled by matching kinetic isotope effects predicted via quantum chemical calculations to intrinsic values. The model provides information on the geometry and electrostatics of the human PNMT transition state structure and indicates that human PNMT catalyzes the formation of epinephrine through an early SN2 transition state in which methyl transfer is rate-limiting.

| S-EPMC5553282 | biostudies-literature

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