Mechanism of eukaryotic serine racemase-catalyzed serine dehydration
Mechanism of eukaryotic serine racemase-catalyzed serine dehydration
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真核丝氨酸消旋酶催化丝氨酸脱水机制
DOI：
10.1016/j.bbapap.2020.140460
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Yoshimura Tohru
中科院分区：
文献类型：
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作者：
Ito Tomokazu;Matsuoka Mai;Goto Masaru;Watanabe Soichiro;Mizobuchi Taichi;Matsushita Kazuma;Nasu Ryoma;Hemmi Hisashi;Yoshimura Tohru
真核丝氨酸消旋酶（SR）是一种折叠Ⅱ型5′-磷酸吡哆醛酶，催化丝氨酸消旋化并合成N-甲基-d-天冬氨酸受体的共激动剂D-丝氨酸。除了外消旋作用外，SR还催化D-和L-Ser脱水为丙酮酸和氨。SR的双功能性被认为对于D-Ser稳态是重要的。SR以几乎相同的效率催化D-和L-Ser的外消旋化。相比之下，SR催化的L-Ser脱水速率远高于D-Ser脱水速率。这引起了SR不催化直接D-Ser脱水和D-Ser首先转化为L-Ser，然后脱水的争论。本文研究了盘基网柄藻SR（DdSR）催化D-和L-Ser脱水的底物和溶剂同位素效应，证明该酶催化D-和L-Ser直接脱水。研究了D. discoideum和小鼠SR表明，SR区分基板配置在C3，但不是在C2。这可能是SR催化L-和D-Ser脱水效率差异的原因。
Eukaryotic serine racemase (SR) is a pyridoxal 5′-phosphate enzyme belonging to the Fold-type II group, which catalyzes serine racemization and is responsible for the synthesis of D-Ser, a co-agonist of theN-methyl-d-aspartate receptor. In addition to racemization, SR catalyzes the dehydration of D- and L-Ser to pyruvate and ammonia. The bifuctionality of SR is thought to be important for D-Ser homeostasis. SR catalyzes the racemization of D- and L-Ser with almost the same efficiency. In contrast, the rate of L-Ser dehydration catalyzed by SR is much higher than that of D-Ser dehydration. This has caused the argument that SR does not catalyze the direct D-Ser dehydration and that D-Ser is first converted to L-Ser, then dehydrated. In this study, we investigated the substrate and solvent isotope effect of dehydration of D- and L-Ser catalyzed by SR fromDictyostelium discoideum(DdSR) and demonstrated that the enzyme catalyzes direct D-Ser dehydration. Kinetic studies of dehydration of four Thr isomers catalyzed byD. discoideumand mouse SRs suggest that SR discriminates the substrate configuration at C3 but not at C2. This is probably the reason for the difference in efficiency between L- and D-Ser dehydration catalyzed by SR.