What question did this study set out to answer?

To investigate the role of the 9-ribose substituent in substrate binding and transition state stabilization during catalysis by adenosine deaminase.

November 15, 1977Biochemistry

Influence of substituent ribose on transition state affinity in reactions catalyzed by adenosine deaminase

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Authors

RWRichard WolfendenUniversity of North Carolina at Chapel Hill DWDavid F. Wentworth GMGordon N. Mitchell

Discussion

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Implication

In vitro biochemical analysis demonstrates that ribose substituents selectively stabilize the transition state of adenosine deaminase, indicating a critical role in catalytic power.

Key Points

To investigate the role of the 9-ribose substituent in substrate binding and transition state stabilization during catalysis by adenosine deaminase.
Measured kinetic rates and apparent binding affinities (Km) for the deamination of adenosine versus adenine catalyzed by calf intestine adenosine deaminase.
Synthesized transition state analogues, including 1,6-dihydro-6-hydroxymethylpurine ribonucleoside and its ribose-deficient counterpart, alongside comparisons with covidarabine and coformycin.
Assayed non-enzymatic model reactions of 6-substituents toward nucleophilic displacement and monitored ultraviolet spectral shifts upon enzyme-inhibitor binding.
Adenosine deaminase hydrolyzed adenine at a limiting rate four orders of magnitude lower than adenosine, despite both substrates exhibiting nearly identical Km values.
Removal of the ribose group from the transition state analogue reduced enzyme binding affinity by several orders of magnitude, while ribose removal had only a slight effect in model displacement reactions.
Binding of transition state analogues and natural inhibitors to the enzyme induced distinct ultraviolet-absorbing bands near 323 nm.

Cite This Study

Wolfenden et al. (1977) studied this question.

synapsesocial.com/papers/6a96aa3f33d7b00ae7bb92d0 https://doi.org/10.1021/bi00642a020

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November 15, 1977Biochemistry

Influence of substituent ribose on transition state affinity in reactions catalyzed by adenosine deaminase

View Full Paper

Ask AI

Bookmark

Authors

RWRichard WolfendenUniversity of North Carolina at Chapel Hill DWDavid F. Wentworth GMGordon N. Mitchell

Discussion

Member takes

Implication

In vitro biochemical analysis demonstrates that ribose substituents selectively stabilize the transition state of adenosine deaminase, indicating a critical role in catalytic power.

Key Points

To investigate the role of the 9-ribose substituent in substrate binding and transition state stabilization during catalysis by adenosine deaminase.
Measured kinetic rates and apparent binding affinities (Km) for the deamination of adenosine versus adenine catalyzed by calf intestine adenosine deaminase.
Synthesized transition state analogues, including 1,6-dihydro-6-hydroxymethylpurine ribonucleoside and its ribose-deficient counterpart, alongside comparisons with covidarabine and coformycin.
Assayed non-enzymatic model reactions of 6-substituents toward nucleophilic displacement and monitored ultraviolet spectral shifts upon enzyme-inhibitor binding.
Adenosine deaminase hydrolyzed adenine at a limiting rate four orders of magnitude lower than adenosine, despite both substrates exhibiting nearly identical Km values.
Removal of the ribose group from the transition state analogue reduced enzyme binding affinity by several orders of magnitude, while ribose removal had only a slight effect in model displacement reactions.
Binding of transition state analogues and natural inhibitors to the enzyme induced distinct ultraviolet-absorbing bands near 323 nm.

Cite This Study

Wolfenden et al. (1977) studied this question.

synapsesocial.com/papers/6a96aa3f33d7b00ae7bb92d0 https://doi.org/10.1021/bi00642a020

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