Mouse brain serine racemase catalyzes specific elimination of L‐serine to pyruvate

FEBS Letters

Bařinka, Cyril²  Majer, Pavel¹  Střı́šovský, Kvido²  Konvalinka, Jan²  Jirásková, Jana²  Slusher, Barbara S¹  Rojas, Camilo¹ 

[1] Guilford Pharmaceuticals Inc., 6610 Tributary Street, Baltimore, MD 21224, USA;Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo n.2, Praha 6, 166 10, Czech Republic

关键词: Serine racemase;    Pyridoxal phosphate;    Pyruvate;    D-Serine;    Glutamate receptor agonist;    mSR;    mouse serine racemase;    PLP;    pyridoxal 5′-phosphate;    NADH;    nicotinamide adenine dinucleotide reduced form;    HEPES;    2-[4-(2-hydroxyethyl)-1-piperazinyl]-ethanesulfonic acid;    EDTA;    ethylenediamine tetraacetic acid;   

DOI  :  10.1016/S0014-5793(02)03855-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Mg²⁺, Ca²⁺ or Mn²⁺ 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.

【 授权许可】

Unknown