6X8Z
Crystal structure of N-truncated human B12 chaperone CblD(C262S)-thiolato-cob(III)alamin complex (108-296)
Summary for 6X8Z
| Entry DOI | 10.2210/pdb6x8z/pdb |
| Descriptor | Methylmalonic aciduria and homocystinuria type D protein, mitochondrial, COBALAMIN (3 entities in total) |
| Functional Keywords | cobalamin, vitamin b12, chaperone, oxidoreductase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 46309.59 |
| Authors | Mascarenhas, R.,Li, Z.,Koutmos, M.,Banerjee, R. (deposition date: 2020-06-02, release date: 2020-09-16, Last modification date: 2023-10-18) |
| Primary citation | 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 Cited by 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: 32871076DOI: 10.1021/jacs.0c06590 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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