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A structural basis for substrate selectivity and stereoselectivity in octopine dehydrogenase from Pecten maximus
Sander H J Smits1, Andre Mueller, Lutz Schmitt
1Institute of Biochemistry, Heinrich Heine University, Universitaetsstrasse 1, 40225 Duesseldorf, Germany.
Journal of Molecular Biology
|July 5, 2008
Summary
Octopine dehydrogenase (OcDH) from scallops uses crystal structures to reveal how it binds substrates like l-arginine and pyruvate. This mechanism ensures selective and stereoselective catalysis for anaerobic energy production.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Octopine dehydrogenase (OcDH) is a key enzyme in anaerobic metabolism in scallops, essential for energy production during strenuous activity.
- OcDH belongs to the opine dehydrogenase (OpDH) family and plays a crucial role in regenerating NAD+ from NADH.
- Unlike other OpDHs, OcDH exhibits strict substrate specificity for l-arginine.
Purpose of the Study:
- To elucidate the structural basis of substrate recognition and binding in OcDH.
- To understand the catalytic mechanism of OcDH, particularly its selectivity and stereoselectivity.
- To provide insights into the enzyme's role in anaerobic ATP provision.
Main Methods:
- X-ray crystallography was employed to determine the crystal structures of OcDH.
- Structures were obtained for OcDH in complex with NADH, and binary complexes with NADH/l-arginine and NADH/pyruvate.
Main Results:
- Detailed structural information was obtained on OcDH complexes, revealing substrate binding principles.
- OcDH utilizes a combination of electrostatic interactions and size selection for substrate binding.
- The enzyme demonstrates high substrate selectivity and stereoselectivity, employing a 'molecular ruler' mechanism.
Conclusions:
- The crystal structures provide a mechanistic understanding of OcDH's substrate specificity and catalytic activity.
- The findings highlight the enzyme's adaptation for efficient anaerobic energy production in scallops.
- OcDH's unique binding and catalytic mechanisms offer insights into enzyme evolution and function.
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