A Noncatalytic Cysteine Residue Modulates Cobalamin Reactivity in the Human B12 Processing Enzyme CblC

Esser AJ, Sastre S, Dinh TJ, Tanner V, Wingert V, Klotz K, Jacobsen DW, Spiekerkoetter U, Schilling O, Zeida A, Radi R, Hannibal L.

Biochemistry. 2025; doi: 10.1021/acs.biochem.4c00613

Cys149 in human CblC modulates B12 processing by reducing unproductive electron transfer. Its substitution (Cys149Ser/Ala) speeds up MeCbl dealkylation but increases GSSG formation. This mirrors C. elegans CblC and reflects adaptation to oxygen-rich environments with low B12 turnover.