A structural basis for substrate selectivity and stereoselectivity in octopine dehydrogenase from Pecten maximus |
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Authors: | Smits Sander H J Mueller Andre Schmitt Lutz Grieshaber Manfred K |
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Affiliation: | 1 Institute of Biochemistry, Heinrich Heine University, Universitaetsstrasse 1, 40225 Duesseldorf, Germany 2 Institute of Zoophysiology, Heinrich Heine University, Universitaetsstrasse 1, 40225 Duesseldorf, Germany |
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Abstract: | Octopine dehydrogenase [N2-(d-1-carboxyethyl)-l-arginine:NAD+ oxidoreductase] (OcDH) from the adductor muscle of the great scallop Pecten maximus catalyzes the reductive condensation of l-arginine and pyruvate to octopine during escape swimming. This enzyme, which is a prototype of opine dehydrogenases (OpDHs), oxidizes glycolytically born NADH to NAD+, thus sustaining anaerobic ATP provision during short periods of strenuous muscular activity. In contrast to some other OpDHs, OcDH uses only l-arginine as the amino acid substrate. Here, we report the crystal structures of OcDH in complex with NADH and the binary complexes NADH/l-arginine and NADH/pyruvate, providing detailed information about the principles of substrate recognition, ligand binding and the reaction mechanism. OcDH binds its substrates through a combination of electrostatic forces and size selection, which guarantees that OcDH catalysis proceeds with substrate selectivity and stereoselectivity, giving rise to a second chiral center and exploiting a “molecular ruler” mechanism. |
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Keywords: | CENDH, N-(1- smallcaps" >d-carboxyethyl)- smallcaps" >l-norvaline: NAD+ oxidoreductase LDH, lactate dehydrogenase MDH, malate dehydrogenase OcDH, octopine dehydrogenase [N2-( smallcaps" >d-1-carboxyethyl)- smallcaps" >l-arginine: NAD+ oxidoreductase] OpDH, opine dehydrogenase SAD, single anomalous dispersion |
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