Fig. 5: Model of assemblies involved in B12 loading and repair. | Nature Communications

Fig. 5: Model of assemblies involved in B12 loading and repair.

From: Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair

Fig. 5

Free MMUT (light and dark blue are the B12 and substrate domains) exists in the “stacked” and “unstacked” conformations with the equilibrium favoring the former [1]. MMAA (yellow) stabilizes the unstacked conformation by wedging between the substrate and B12 domains and itself transitions from an “open” to “closed” state in M2C2, crystallized in this study (red box) [2]. MMAB transfers AdoCbl to M2C2 [3], leading to catalytically active holo-MMUT [4]. In vitro, free AdoCbl can bind to MMUT [4′]. Inactivation of MMUT due to loss of Ado (deoxyadenosine) followed by ADP binding, stabilizes cob(II)alamin against hyperoxidation [5] and leads to recruitment of the repair complex [6] and [7]. Following cob(II)alamin off-loading and conversion to AdoCbl by MMAB, the active cofactor is reloaded onto MMUT [8].

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