Structure of putative tumor suppressor ALDH1L1.
Structure of putative tumor suppressor ALDH1L1.
复制标题
推定的肿瘤抑制因子ALDH1L1的结构。
DOI：
10.1038/s42003-021-02963-9
复制
发表时间：
2022-01-10
影响因子：
5.9
通讯作者：
Krupenko SA
中科院分区：
文献类型：
--
作者：
Tsybovsky Y;Sereda V;Golczak M;Krupenko NI;Krupenko SA
假定的肿瘤抑制因子ALDH 1 L1是三个不相关基因自然融合的产物，通过催化NADP+依赖性的10-甲酰四氢叶酸转化为四氢叶酸和CO2来调节叶酸代谢。四聚体大鼠ALDH 1 L1的Cryo-EM结构揭示了这种复杂酶的结构和功能域相互作用。高移动的N-末端结构域，其从10-甲酰四氢叶酸中除去甲酰，经历多个瞬时结构域间相互作用。将甲酰基转化为CO2的C-末端醛脱氢酶结构域与中间结构域（酰基/肽基载体蛋白（A/PCP）的同系物）形成异常大的界面，所述中间结构域在催化结构域之间转移甲酰基。中间结构域的4′-磷酸泛酰巯基乙胺臂完全延伸并深入C末端结构域的催化口袋。值得注意的是，ALDH 1 L1的四聚体状态对于催化是必不可少的，因为中间结构域在不同原异构体的催化结构域之间转移甲酰基。这些发现强调了A/PCPs在复杂的、高度动态的酶系统中的多功能性。齐博夫斯基等等人报道了四聚体大鼠ALDH 1 L1的cryo-EM结构，阐明了其结构和对其功能重要的结构域相互作用。这些发现强调了酰基/肽基载体蛋白在复杂的、高度动态的酶系统中的多功能性。
Putative tumor suppressor ALDH1L1, the product of natural fusion of three unrelated genes, regulates folate metabolism by catalyzing NADP+-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2. Cryo-EM structures of tetrameric rat ALDH1L1 revealed the architecture and functional domain interactions of this complex enzyme. Highly mobile N-terminal domains, which remove formyl from 10-formyltetrahydrofolate, undergo multiple transient inter-domain interactions. The C-terminal aldehyde dehydrogenase domains, which convert formyl to CO2, form unusually large interfaces with the intermediate domains, homologs of acyl/peptidyl carrier proteins (A/PCPs), which transfer the formyl group between the catalytic domains. The 4′-phosphopantetheine arm of the intermediate domain is fully extended and reaches deep into the catalytic pocket of the C-terminal domain. Remarkably, the tetrameric state of ALDH1L1 is indispensable for catalysis because the intermediate domain transfers formyl between the catalytic domains of different protomers. These findings emphasize the versatility of A/PCPs in complex, highly dynamic enzymatic systems. Tsybovsky et. al. report cryo-EM structures of tetrameric rat ALDH1L1 elucidating its architecture and domain interactions important for its functions. These findings emphasize the versatility of acyl/peptidyl carrier proteins in complex, highly dynamic enzymatic systems.
登录
查看更多内容
DOI：
10.1107/s2059798318009324
发表时间：
2018-09-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Afonine PV;Klaholz BP;Moriarty NW;Poon BK;Sobolev OV;Terwilliger TC;Adams PD;Urzhumtsev A
通讯作者：
Urzhumtsev A
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Beniaminov AD;Puzanov GA;Krasnov GS;Kaluzhny DN;Kazubskaya TP;Braga EA;Kudryavtseva AV;Melnikova NV;Dmitriev AA
通讯作者：
Dmitriev AA
影响因子：
4.8
作者：
Chumanevich, AA;Krupenko, SA;Davies, C
通讯作者：
Davies, C
DOI：
10.1073/pnas.0805983105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Cryle, Max J.;Schlichting, Ilme
通讯作者：
Schlichting, Ilme