6D5K

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

6D5K の概要

• エントリーDOI: 10.2210/pdb6d5k/pdb
• 分子名称: Cob(I)yrinic acid a,c-diamide adenosyltransferase, mitochondrial, 5'-DEOXYADENOSINE, COBALAMIN, ... (8 entities in total)
• 機能のキーワード: b12, metabolism, adenosyltransferase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 69695.75

構造登録者

Dodge, G.J.,Campanello, G.,Smith, J.L.,Banerjee, R. (登録日: 2018-04-19, 公開日: 2018-10-10, 最終更新日: 2023-10-04)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.85 Å)