5uos
From Proteopedia
Crystal Structure of CblC (MMACHC) (1-238), a human B12 processing enzyme, complexed with an Antivitamin B12
Structural highlights
DiseaseMMAC_HUMAN Methylmalonic acidemia with homocystinuria, type cblC. The disease is caused by mutations affecting the gene represented in this entry. FunctionMMAC_HUMAN May be involved in the binding and intracellular trafficking of cobalamin (vitamin B12). Publication Abstract from PubMedB12 antivitamins are important and robust tools for investigating the biological roles of vitamin B12 . Here, the potential antivitamin B12 2,4-difluorophenylethynylcobalamin (F2PhEtyCbl) was prepared, and its 3D structure was studied in solution and in the crystal. Chemically inert F2PhEtyCbl resisted thermolysis of its Co-C bond at 100 degrees C, was stable in bright daylight, and also remained intact upon prolonged storage in aqueous solution at room temperature. It binds to the human B12 -processing enzyme CblC with high affinity (KD =130 nm) in the presence of the cosubstrate glutathione (GSH). F2PhEtyCbl withstood tailoring by CblC, and it also stabilized the ternary complex with GSH. The crystal structure of this inactivated assembly provides first insight into the binding interactions between an antivitamin B12 and CblC, as well as into the organization of GSH and a base-off cobalamin in the active site of this enzyme. Antivitamin B12 Inhibition of the Human B12 -Processing Enzyme CblC: Crystal Structure of an Inactive Ternary Complex with Glutathione as the Cosubstrate.,Ruetz M, Shanmuganathan A, Gherasim C, Karasik A, Salchner R, Kieninger C, Wurst K, Banerjee R, Koutmos M, Krautler B Angew Chem Int Ed Engl. 2017 Jun 19;56(26):7387-7392. doi:, 10.1002/anie.201701583. Epub 2017 May 23. PMID:28544088[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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