从大鼠的肝脏丝氨酸脱水酶的晶体结构。

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山田T, Komoto J,中国人Y,小川H,皮托管HC, Takusagawa F

从大鼠的肝脏丝氨酸脱水酶的晶体结构。

生物化学。2003年11月11日,42 (44):12854 - 65。

PubMed ID

14596599 (在PubMed

]

文摘

SDH (L-serine脱水酶,EC 4.3.1.17)催化5 '磷酸吡哆醛(PLP)端依赖脱水L-serine产生丙酮酸和氨。肝脏SDH在糖质新生扮演着重要的角色。SDH是一个两步反应形成丙酮酸的丝氨酸的羟基产生aminoacrylate裂解,然后aminoacrylate由非酶的水解产生丙酮酸脱氨基。鼠肝脏apo-SDH的晶体结构是由单一同形替代2.8一项决议。与O-methylserine holo-SDH结晶(OMS)也在2.6决议确定分子替换。SDH是由两个域,每个域有一个典型的alphabeta-open结构。活动地点位于两个域之间的间隙。holo-SDH包含PLP-OMS醛亚胺活性部位,表明OMS可以用PLP形成席夫碱的链接,但随后脱水并没有发生。Apo-SDH小域插入形成二聚体的催化裂伙伴亚基,这样活跃的网站关闭。Holo-SDH也形成一个二聚体通过接触的结晶,使二聚不关闭催化裂。 The phosphate group of PLP is surrounded by a characteristic G-rich sequence ((168)GGGGL(172)) and forms hydrogen bonds with the amide groups of those amino acid residues, suggesting that the phosphate group can be protonated. N(1) of PLP participates in a hydrogen bond with Cys303, and similar hydrogen bonds with N(1) participating are seen in other beta-elimination enzymes. These hydrogen bonding schemes indicate that N(1) is not protonated, and thus, the pyridine ring cannot take a quinone-like structure. These characteristics of the bound PLP suggest that SDH catalysis is not facilitated by forming the resonance-stabilized structure of the PLP-Ser aldimine as seen in aminotransferases. A possible catalytic mechanism involves the phosphate group, surrounded by the characteristic sequence, acting as a general acid to donate a proton to the leaving hydroxyl group of serine.

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药物靶点

药物	目标	类	生物	药理作用	行动
磷酸吡哆醛	L-serine脱水酶/苏氨酸脱氨酶	蛋白质	人类	未知的	代数余子式	细节