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Enzyme Speed Limits
How Fast Can Enzymes Really Go?
| One of the most fundamental processes in biology is RNA degradation. This process occurs spontaneously with a half life for cleavage of a typical RNA linkage under cell like conditions of approximately one year. In contrast, some enzymes can cleave RNA linkages with speeds that approach 100,000 per minute. Interestingly, scientists have yet to reach consensus on how enzymes achieve these extraordinary rate enhancements. Researchers in the Breaker lab have generated many new and simple examples of ribozymes and deoxyribozymes that cleave RNA. These and other enzymes are being used to investigate catalysis of RNA cleavage by transesterification. Combined with natural examples, there are now more than two dozen ribozymes and deoxyribozymes that catalyze this reaction. In addition, we have studied RNA transesterification by the non-enzymatic processes of internucleotide linkage geometric alignment and specific base catalysis.
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Using these approaches, we have
embarked on a program to explore basic principles of enzyme function
by comparative analysis. After consideration of additional data
regarding specific acid catalysis and cleavage of RNA analogs, we
have constructed a theoretical framework for assessing enzyme me
chanisms based on the use of four key catalytic strategies: proper
geometric alignment ( We expect that these efforts will find utility in explaining the behavior of other enzymes as well. Our findings from these types of analyses indicate that both RNA and DNA enzymes could be made to catalyze reactions with speeds that are similar to those achieved by protein enzymes. We predict that this theory of catalytic mechanism can be used to develop high-speed ribozymes and deoxyribozymes efficiently for practical application.
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),
neutralization of non-esterified oxygen negative charge (
),
activation of the nucleophile (
),
and neutralization of leaving group negative charge (
).
Email:
Ronald Breaker
Office: (203) 432-9389
Lab: (203) 432-6554
Fax: (203) 432-6161
| Images and Design Copyright 2003 |
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Last Updated 06/2003 |