6x8z
From Proteopedia
Crystal structure of N-truncated human B12 chaperone CblD(C262S)-thiolato-cob(III)alamin complex (108-296)
Structural highlights
DiseaseMMAD_HUMAN Methylcobalamin deficiency type cblDv1;Methylmalonic acidemia with homocystinuria, type cblD;Vitamin B12-responsive methylmalonic acidemia, type cblDv2. The disease is caused by mutations affecting the gene represented in this entry. FunctionMMAD_HUMAN Involved in cobalamin metabolism.[1] Publication Abstract from PubMedThe 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. An Interprotein Co-S Coordination Complex in the B12-Trafficking Pathway.,Li Z, Mascarenhas R, Twahir UT, Kallon A, Deb A, Yaw M, Penner-Hahn J, Koutmos M, Warncke K, Banerjee R J Am Chem Soc. 2020 Sep 14. doi: 10.1021/jacs.0c06590. PMID:32871076[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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