5UJC

Crystal structure of a C.elegans B12-trafficking protein CblC, a human MMACHC homologue

5UJC の概要

• エントリーDOI: 10.2210/pdb5ujc/pdb
• 分子名称: MMACHC-like protein, CO-METHYLCOBALAMIN, L(+)-TARTARIC ACID, ... (6 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: Caenorhabditis elegans
• 細胞内の位置: Cytoplasm : Q7Z144
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33238.43

構造登録者

Li, Z.,Shanmuganathan, A.,Ruetz, M.,Yamada, K.,Lesniak, N.A.,Krautler, B.,Brunold, T.C.,Banerjee, R.,Koutmos, M. (登録日: 2017-01-17, 公開日: 2017-05-03, 最終更新日: 2023-10-04)

主引用文献

Li, Z.,Shanmuganathan, A.,Ruetz, M.,Yamada, K.,Lesniak, N.A.,Krautler, B.,Brunold, T.C.,Koutmos, M.,Banerjee, R.
Coordination chemistry controls the thiol oxidase activity of the B12-trafficking protein CblC.
J. Biol. Chem., 292:9733-9744, 2017

PubMed Abstract: The cobalamin or B cofactor supports sulfur and one-carbon metabolism and the catabolism of odd-chain fatty acids, branched-chain amino acids, and cholesterol. CblC is a B-processing enzyme involved in an early cytoplasmic step in the cofactor-trafficking pathway. It catalyzes the glutathione (GSH)-dependent dealkylation of alkylcobalamins and the reductive decyanation of cyanocobalamin. CblC from (CblC) also exhibits a robust thiol oxidase activity, converting reduced GSH to oxidized GSSG with concomitant scrubbing of ambient dissolved O The mechanism of thiol oxidation catalyzed by CblC is not known. In this study, we demonstrate that novel coordination chemistry accessible to CblC-bound cobalamin supports its thiol oxidase activity via a glutathionyl-cobalamin intermediate. Deglutathionylation of glutathionyl-cobalamin by a second molecule of GSH yields GSSG. The crystal structure of CblC provides insights into how architectural differences at the α- and β-faces of cobalamin promote the thiol oxidase activity of CblC but mute it in wild-type human CblC. The R161G and R161Q mutations in human CblC unmask its latent thiol oxidase activity and are correlated with increased cellular oxidative stress disease. In summary, we have uncovered key architectural features in the cobalamin-binding pocket that support unusual cob(II)alamin coordination chemistry and enable the thiol oxidase activity of CblC.

PubMed: 28442570
DOI: 10.1074/jbc.M117.788554

実験手法

X-RAY DIFFRACTION (1.35 Å)