6X8Z

Crystal structure of N-truncated human B12 chaperone CblD(C262S)-thiolato-cob(III)alamin complex (108-296)

6X8Z の概要

• エントリーDOI: 10.2210/pdb6x8z/pdb
• 分子名称: Methylmalonic aciduria and homocystinuria type D protein, mitochondrial, COBALAMIN (3 entities in total)
• 機能のキーワード: cobalamin, vitamin b12, chaperone, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46309.59

構造登録者

Mascarenhas, R.,Li, Z.,Koutmos, M.,Banerjee, R. (登録日: 2020-06-02, 公開日: 2020-09-16, 最終更新日: 2023-10-18)

主引用文献

Li, Z.,Mascarenhas, R.,Twahir, U.T.,Kallon, A.,Deb, A.,Yaw, M.,Penner-Hahn, J.,Koutmos, M.,Warncke, K.,Banerjee, R.
An Interprotein Co-S Coordination Complex in the B 12 -Trafficking Pathway.
J.Am.Chem.Soc., 142:16334-16345, 2020

PubMed Abstract: The CblC and CblD chaperones are involved in early steps in the cobalamin trafficking pathway. Cobalamin derivatives entering the cytoplasm are converted by CblC to a common cob(II)alamin intermediate via glutathione-dependent alkyltransferase or reductive elimination activities. Cob(II)alamin is subsequently converted to one of two biologically active alkylcobalamins by downstream chaperones. The function of CblD has been elusive although it is known to form a complex with CblC under certain conditions. Here, we report that CblD provides a sulfur ligand to cob(II)alamin bound to CblC, forming an interprotein coordination complex that rapidly oxidizes to thiolato-cob(III)alamin. Cysteine scanning mutagenesis and EPR spectroscopy identified Cys-261 on CblD as the sulfur donor. The unusual interprotein Co-S bond was characterized by X-ray absorption spectroscopy and visualized in the crystal structure of the human CblD thiolato-cob(III)alamin complex. Our study provides insights into how cobalamin coordination chemistry could be utilized for cofactor translocation in the trafficking pathway.

PubMed: 32871076
DOI: 10.1021/jacs.0c06590

実験手法

X-RAY DIFFRACTION (2.5 Å)