Mouse brain serine racemase catalyzes specific elimination of L-serine to pyruvate.
D-Serine was previously identified in mammalian brain and was shown to be a co-agonist at the 'glycine' site of the N-methyl-D-aspartate (NMDA)-type receptors. Racemization of serine is catalyzed by serine racemase, a pyridoxal 5'-phosphate-dependent enzyme expressed mainly in brain and liver. NMDA receptor overactivation has been implicated in a number of pathological conditions and inhibitors of serine racemase are thus potentially interesting targets for therapy. We expressed recombinant mouse serine racemase in insect cells and purified it to near homogeneity. The enzyme is a non-covalent homodimer in solution and requires divalent cations Mg(2+), Ca(2+) or Mn(2+) for activity but not for dimerization. In addition to the racemization it also catalyzes specific elimination of L-Ser to pyruvate. D-Serine is eliminated much less efficiently. Both L-serine racemization and elimination activities of serine racemase are of comparable magnitude, display alkaline pH optimum and are negligible below pH 6.5.
Strísovský
Kvido
K
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo n.2, Praha 6, 166 10, Czech Republic. kvido.strisovsky@uochb.cas.cz
Jirásková
Jana
J
Barinka
Cyril
C
Majer
Pavel
P
Rojas
Camilo
C
Slusher
Barbara S
BS
Konvalinka
Jan
J
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002384:Catalysis; D002413:Cations, Divalent / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D019281:Dimerization; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D051379:Mice; D019289:Pyruvic Acid / Q000378:metabolism*; D019998:Racemases and Epimerases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D013379:Substrate Specificity; D000099300:Serine Racemase
D002413:Cations, Divalent; D019289:Pyruvic Acid; D019998:Racemases and Epimerases; D011994:Recombinant Proteins; D012694:Serine; D000099300:Serine Racemase