3sc0

Crystal Structure of MMACHC (1-238), a human B12 processing enzyme, complexed with MethylCobalamin

spinqualitylabelsall models 3sc0, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3sc0 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease MMAC_HUMAN Methylmalonic acidemia with homocystinuria, type cblC. The disease is caused by mutations affecting the gene represented in this entry. Function MMAC_HUMAN May be involved in the binding and intracellular trafficking of cobalamin (vitamin B12). Publication Abstract from PubMed An early step in the intracellular processing of B12 involves CblC, which exhibits dual reactivity, catalyzing the reductive decyanation of cyanocobalamin (vitamin B12) and the dealkylation of alkylcobalamins (e.g. methylcobalamin; MeCbl). Insights into how the CblC scaffold supports this chemical dichotomy have been unavailable despite it being the most common locus of patient mutations associated with inherited cobalamin disorders that manifest in both severe homocystinuria and methylmalonic aciduria. Herein, we report structures of human CblC, with and without bound MeCbl, which provide novel biochemical insights into its mechanism of action. Our results reveal that CblC is the most divergent member of the NADPH-dependent flavin reductase family and can use FMN or FAD as a prosthetic group to catalyze reductive decyanation. Furthermore, CblC is the first example of an enzyme with glutathione transferase activity that has a sequence and structure unrelated to the GST superfamily. CblC thus represents an example of evolutionary adaptation of a common structural platform to perform diverse chemistries. The CblC structure allows us to rationalize the biochemical basis of a number of pathological mutations associated with severe clinical phenotypes. The structural basis of multifunctionality in a B12 processing enzyme.,Koutmos M, Gherasim C, Smith JL, Banerjee R J Biol Chem. 2011 Jun 22. PMID:21697092 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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