Transition state analogues for enzymes of nucleic acid metabolism.

Research output: Chapter in Book/Report/Conference proceedingChapter

10 Citations (Scopus)

Abstract

Knowledge of enzymatic transition states permits the logical design of transition state analogues. Kinetic isotope effects have been used to solve transition state structures for several N-ribosyltransferases. Nucleoside hydrolases from protozoan parasites show ribooxacarbenium ion character at their transition states, but with different extents of activation at the leaving group and the oxacarbenium ion. Transition state analogues are designed to capture these interactions and provide isozyme-specific inhibitors. Ricin A-chain is an RNA N-ribohydrolase for a single site on 28S rRNA. Its transition state resembles a fully dissociated ribooxacarbenium ion. A transition state analogue for ricin A-chain mimics the fully dissociated purine and cationic ribosyl transition state. The transition state for human purine nucleoside phosphorylase (PNP) is more dissociated than for the bovine enzyme. Immucillin-H, a powerful transition state inhibitor for human PNP, has entered clinical trials as an anti T-cell agent.

Original languageEnglish (US)
Title of host publicationNucleic acids research. Supplement (2001)
Pages107-108
Number of pages2
Edition3
StatePublished - 2003

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Purine-Nucleoside Phosphorylase
Nucleic Acids
Ricin
Ions
Enzymes
N-Glycosyl Hydrolases
Isotopes
Isoenzymes
Parasites
Clinical Trials
RNA
T-Lymphocytes
purine
forodesine
Thomsen-Friedenreich antibodies

Cite this

Schramm, V. L. (2003). Transition state analogues for enzymes of nucleic acid metabolism. In Nucleic acids research. Supplement (2001) (3 ed., pp. 107-108)

Transition state analogues for enzymes of nucleic acid metabolism. / Schramm, Vern L.

Nucleic acids research. Supplement (2001). 3. ed. 2003. p. 107-108.

Research output: Chapter in Book/Report/Conference proceedingChapter

Schramm, VL 2003, Transition state analogues for enzymes of nucleic acid metabolism. in Nucleic acids research. Supplement (2001). 3 edn, pp. 107-108.
Schramm VL. Transition state analogues for enzymes of nucleic acid metabolism. In Nucleic acids research. Supplement (2001). 3 ed. 2003. p. 107-108
Schramm, Vern L. / Transition state analogues for enzymes of nucleic acid metabolism. Nucleic acids research. Supplement (2001). 3. ed. 2003. pp. 107-108
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