5UOS

Crystal Structure of CblC (MMACHC) (1-238), a human B12 processing enzyme, complexed with an Antivitamin B12

5UOS の概要

• エントリーDOI: 10.2210/pdb5uos/pdb
• 分子名称: Methylmalonic aciduria and homocystinuria type C protein, COBALAMIN, 1-ethynyl-2,4-difluorobenzene, ... (8 entities in total)
• 機能のキーワード: vitamin b12, oxidoreductase, b12 trafficking, b12 processing, b12 binding
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : Q9Y4U1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29681.66

構造登録者

Shanmuganathan, A.,Karasik, A.,Ruetz, M.,Banerjee, R.,Krautler, B.,Koutmos, M. (登録日: 2017-02-01, 公開日: 2017-06-07, 最終更新日: 2023-10-04)

主引用文献

Ruetz, M.,Shanmuganathan, A.,Gherasim, C.,Karasik, A.,Salchner, R.,Kieninger, C.,Wurst, K.,Banerjee, R.,Koutmos, M.,Krautler, B.
Antivitamin B12 Inhibition of the Human B12 -Processing Enzyme CblC: Crystal Structure of an Inactive Ternary Complex with Glutathione as the Cosubstrate.
Angew. Chem. Int. Ed. Engl., 56:7387-7392, 2017

PubMed Abstract: B antivitamins are important and robust tools for investigating the biological roles of vitamin B . Here, the potential antivitamin B 2,4-difluorophenylethynylcobalamin (F2PhEtyCbl) was prepared, and its 3D structure was studied in solution and in the crystal. Chemically inert F2PhEtyCbl resisted thermolysis of its Co-C bond at 100 °C, was stable in bright daylight, and also remained intact upon prolonged storage in aqueous solution at room temperature. It binds to the human B -processing enzyme CblC with high affinity (K =130 nm) in the presence of the cosubstrate glutathione (GSH). F2PhEtyCbl withstood tailoring by CblC, and it also stabilized the ternary complex with GSH. The crystal structure of this inactivated assembly provides first insight into the binding interactions between an antivitamin B and CblC, as well as into the organization of GSH and a base-off cobalamin in the active site of this enzyme.

PubMed: 28544088
DOI: 10.1002/anie.201701583

実験手法

X-RAY DIFFRACTION (2.51 Å)