6D5X

Structure of Human ATP:Cobalamin Adenosyltransferase bound to ATP, Adenosylcobalamin, and Triphosphate

Summary for 6D5X

• Entry DOI: 10.2210/pdb6d5x/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: 69643.64

Authors

Dodge, G.J.,Campanello, G.,Smith, J.L.,Banerjee, R. (deposition date: 2018-04-19, release date: 2018-10-10, Last modification date: 2024-03-13)

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

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: 30282455
DOI: 10.1021/jacs.8b08659

Experimental method

X-RAY DIFFRACTION (2.4 Å)