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Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by a terpenoid cyclase
Douglas A Whittington1, Mitchell L Wise, Marek Urbansky
1Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, USA.
Summary
Researchers determined the structure of (+)-bornyl diphosphate synthase, a key enzyme in monoterpene biosynthesis. This structure reveals how the enzyme catalyzes reactions by stabilizing crucial carbocation intermediates during terpene cyclization.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Monoterpene cyclases are crucial enzymes in the biosynthesis of terpenes.
- Salvia officinalis (+)-bornyl diphosphate synthase is a metal-requiring monoterpene cyclase.
Purpose of the Study:
- To determine the x-ray crystal structure of dimeric (+)-bornyl diphosphate synthase.
- To elucidate the catalytic mechanism of terpene cyclization by stabilizing carbocation intermediates.
Main Methods:
- X-ray crystallography at 2.0-A resolution.
- Structure determination of enzyme complexes with substrate analogues and intermediates.
Main Results:
- The dimeric structure reveals two alpha-helical domains per monomer.
- The C-terminal domain contains the active site responsible for geranyl diphosphate cyclization.
- The N-terminal domain's role is less defined but may influence catalysis by capping the active site.
- Complex structures provide insights into the stabilization of carbocation intermediates.
Conclusions:
- The structure of (+)-bornyl diphosphate synthase provides a detailed view of the terpene cyclization cascade.
- Understanding the enzyme's mechanism can aid in the design of novel catalysts and drugs.