6D5K
Structure of Human ATP:Cobalamin Adenosyltransferase bound to ATP, and Adenosylcobalamin
Summary for 6D5K
| Entry DOI | 10.2210/pdb6d5k/pdb |
| Descriptor | Cob(I)yrinic acid a,c-diamide adenosyltransferase, mitochondrial, 5'-DEOXYADENOSINE, COBALAMIN, ... (8 entities in total) |
| Functional Keywords | b12, metabolism, adenosyltransferase, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 3 |
| Total formula weight | 69695.75 |
| Authors | Dodge, G.J.,Campanello, G.,Smith, J.L.,Banerjee, R. (deposition date: 2018-04-19, release date: 2018-10-10, Last modification date: 2023-10-04) |
| Primary citation | Campanello, G.C.,Ruetz, M.,Dodge, G.J.,Gouda, H.,Gupta, A.,Twahir, U.T.,Killian, M.M.,Watkins, D.,Rosenblatt, D.S.,Brunold, T.C.,Warncke, K.,Smith, J.L.,Banerjee, R. Sacrificial Cobalt-Carbon Bond Homolysis in Coenzyme B12as a Cofactor Conservation Strategy. J. Am. Chem. Soc., 140:13205-13208, 2018 Cited by PubMed Abstract: A sophisticated intracellular trafficking pathway in humans is used to tailor vitamin B into its active cofactor forms, and to deliver it to two known B-dependent enzymes. Herein, we report an unexpected strategy for cellular retention of B, an essential and reactive cofactor. If methylmalonyl-CoA mutase is unavailable to accept the coenzyme B product of adenosyltransferase, the latter catalyzes homolytic scission of the cobalt-carbon bond in an unconventional reversal of the nucleophilic displacement reaction that was used to make it. The resulting homolysis product binds more tightly to adenosyltransferase than does coenzyme B, facilitating cofactor retention. We have trapped, and characterized spectroscopically, an intermediate in which the cobalt-carbon bond is weakened prior to being broken. The physiological relevance of this sacrificial catalytic activity for cofactor retention is supported by the significantly lower coenzyme B concentration in patients with dysfunctional methylmalonyl-CoA mutase but normal adenosyltransferase activity. PubMed: 30282455DOI: 10.1021/jacs.8b08659 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.85 Å) |
Structure validation
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