Insights into the Mechanism of Ligand Binding to Octopine Dehydrogenase from Pecten maximus by NMR and Crystallography |
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| Authors: | Sander H. J. Smits Tatu Meyer Andre Mueller Nadine van Os Matthias Stoldt Dieter Willbold Lutz Schmitt Manfred K. Grieshaber |
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| Affiliation: | 1. Institute of Biochemistry, Heinrich-Heine-University, Duesseldorf, Germany.; 2. Institute of Zoophysiology, Heinrich-Heine-University, Duesseldorf, Germany.; 3. Institute of Physical Biology, Heinrich-Heine-University, Duesseldorf, Germany.; 4. Institute of Structural Biology and Biophysics (ISB-3), Research Centre Jülich, Jülich, Germany.;Massachusetts Institute of Technology, United States of America |
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| Abstract: | Octopine dehydrogenase (OcDH) from the adductor muscle of the great scallop, Pecten maximus, catalyzes the NADH dependent, reductive condensation of L-arginine and pyruvate to octopine, NAD+, and water during escape swimming and/or subsequent recovery. The structure of OcDH was recently solved and a reaction mechanism was proposed which implied an ordered binding of NADH, L-arginine and finally pyruvate. Here, the order of substrate binding as well as the underlying conformational changes were investigated by NMR confirming the model derived from the crystal structures. Furthermore, the crystal structure of the OcDH/NADH/agmatine complex was determined which suggests a key role of the side chain of L-arginine in protein cataylsis. Thus, the order of substrate binding to OcDH as well as the molecular signals involved in octopine formation can now be described in molecular detail. |
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