5UOS

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

Summary for 5UOS

• Entry DOI: 10.2210/pdb5uos/pdb
• Descriptor: Methylmalonic aciduria and homocystinuria type C protein, COBALAMIN, 1-ethynyl-2,4-difluorobenzene, ... (8 entities in total)
• Functional Keywords: vitamin b12, oxidoreductase, b12 trafficking, b12 processing, b12 binding
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q9Y4U1
• Total number of polymer chains: 1
• Total formula weight: 29681.66

Authors

Shanmuganathan, A.,Karasik, A.,Ruetz, M.,Banerjee, R.,Krautler, B.,Koutmos, M. (deposition date: 2017-02-01, release date: 2017-06-07, Last modification date: 2023-10-04)

Primary citation

Ruetz, M.,Shanmuganathan, A.,Gherasim, C.,Karasik, A.,Salchner, R.,Kieninger, C.,Wurst, K.,Banerjee, R.,Koutmos, M.,Krautler, B.
Antivitamin B12 Inhibition of the Human B12 -Processing Enzyme CblC: Crystal Structure of an Inactive Ternary Complex with Glutathione as the Cosubstrate.
Angew. Chem. Int. Ed. Engl., 56:7387-7392, 2017

PubMed Abstract: B antivitamins are important and robust tools for investigating the biological roles of vitamin B . Here, the potential antivitamin B 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 °C, was stable in bright daylight, and also remained intact upon prolonged storage in aqueous solution at room temperature. It binds to the human B -processing enzyme CblC with high affinity (K =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 B and CblC, as well as into the organization of GSH and a base-off cobalamin in the active site of this enzyme.

PubMed: 28544088
DOI: 10.1002/anie.201701583

Experimental method

X-RAY DIFFRACTION (2.51 Å)