结构测定和生化研究芽孢杆菌stearothermophilus E53Q丝氨酸hydroxymethyltransferase及其复合物提供见解在功能和酶的记忆里。

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拉贾拉姆V, Bhavani BS, Kaul P, V普拉卡什,Appaji Rao N, Savithri HS,没吃

结构测定和生化研究芽孢杆菌stearothermophilus E53Q丝氨酸hydroxymethyltransferase及其复合物提供见解在功能和酶的记忆里。

2月j . 2007年8月,274 (16):4148 - 60。Epub 2007 7月25。

PubMed ID

17651438 (在PubMed

]

文摘

丝氨酸hydroxymethyltransferase (SHMT)属于alpha-family吡哆醛5 ' -phosphate-dependent酶和催化条件下的可逆转换和tetrahydrofolate g和5,10-methylene tetrahydrofolate。5,10-Methylene tetrahydrofolate作为一个碳碎片的来源在许多生物过程。SHMT也催化tetrahydrofolate-independent L-allo-Thr转换成通用电气和乙醛。芽孢杆菌的晶体结构stearothermophilus SHMT (bsSHMT)建议E53与底物相互作用,自旋和tetrahydrofolate。阐明E53的角色,是突变Q和结构和生化突变酶进行了研究。E53QbsSHMT的内部醛亚胺结构类似于野生型酶,除了在Q53显著变化,60 Y61。g的羧基和侧链的条件下两种构象在各自的外部醛亚胺结构。tetrahydrofolate-dependent乳沟的突变酶完全不活跃的条件,而有增加1.5倍的速度与L-allo-Thr tetrahydrofolate-independent反应。这些研究的结果表明,E53中扮演着重要的角色在tetrahydrofolate / 5-formyl tetrahydrofolate绑定和Cbeta正确定位的条件下的直接攻击tetrahydrofolate的它们。最有趣的是,复杂的结构得到了共结晶的E53QbsSHMT g和5-formyl tetrahydrofolate透露5 '磷酸吡哆醛的gem-diamine形式绑定到g和活跃网站赖氨酸。 However, density for 5-formyl tetrahydrofolate was not observed. Gly carboxylate was in a single conformation, whereas pyridoxal 5'-phosphate had two distinct conformations. The differences between the structures of this complex and Gly external aldimine suggest that the changes induced by initial binding of 5-formyl tetrahydrofolate are retained even though 5-formyl tetrahydrofolate is absent in the final structure. Spectral studies carried out with this mutant enzyme also suggest that 5-formyl tetrahydrofolate binds to the E53QbsSHMT-Gly complex forming a quinonoid intermediate and falls off within 4 h of dialysis, leaving behind the mutant enzyme in the gem-diamine form. This is the first report to provide direct evidence for enzyme memory based on the crystal structure of enzyme complexes.

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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	丝氨酸hydroxymethyltransferase,线粒体	蛋白质	人类	未知的	代数余子式	细节
四氢叶酸	丝氨酸hydroxymethyltransferase,线粒体	蛋白质	人类	未知的	代数余子式	细节