Irreversible inhibition of S-adenosylhomocysteine hydrolase by nucleoside analogs

Peter K. Chiang, Andrzej Guranowski, Jeffrey E. Segall

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

A large number of nucleoside analogs have been found to inactivate S-adenosylhomocysteine (AdoHcy) hydrolase in a time-dependent irreversible manner. There are two classes of these irreversible inhibitors: (A) analogs that inactivate the enzyme in a pseudofirst-order process and are devoid of any side chain at the 5′-OH group; (B) analogs that inactivate the enzyme in a time-dependent but curvilinear process, and generally have a side chain at the 5′ position. Among the more potent irreversible inhibitors are 2-chloroadenosine, 9-β-d-arabinofuranosyladenine (Ara-A), and (±)aristeromycin. Release of adenine base from adenosine or Ara-A in the presence of AdoHcy hydrolase was observed, thus supporting the proposed catalytic mechanism of AdoHcy hydrolase, that entails the transient formation of 3′-ketoadenosine during enzymatic catalysis of either the formation or hydrolysis of AdoHcy. Both Ara-A and adenosine may exert their irreversible inactivation by a suicide mechanism, but nucleosides such as 5′-iodo-5′-deoxyadenosine and 3′-deoxyadenosine are probably strictly irreversible inhibitors per se in view of the catalytic mechanism proposed for AdoHcy hydrolase. Labeling of AdoHcy hydrolase, perhaps covalent in nature, by radioactive Ara-A and adenosine was demonstrated by gel electrophoresis.

Original languageEnglish (US)
Pages (from-to)175-184
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume207
Issue number1
DOIs
StatePublished - 1981
Externally publishedYes

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Adenosylhomocysteinase
Vidarabine
Nucleosides
Hydrolases
Adenosine
2-Chloroadenosine
Adenine
Enzymes
Electrophoresis
Catalysis
Suicide
Labeling
Hydrolysis
Gels
Inhibition (Psychology)

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Irreversible inhibition of S-adenosylhomocysteine hydrolase by nucleoside analogs. / Chiang, Peter K.; Guranowski, Andrzej; Segall, Jeffrey E.

In: Archives of Biochemistry and Biophysics, Vol. 207, No. 1, 1981, p. 175-184.

Research output: Contribution to journalArticle

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