Bradley Justin M, Svistunenko Dimitri A, Lawson Tamara L, Hemmings Andrew M, Moore Geoffrey R, Le Brun Nick E
Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ (UK).
School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ (UK).
Angew Chem Weinheim Bergstr Ger. 2015 Dec 1;127(49):14976-14980. doi: 10.1002/ange.201507486. Epub 2015 Oct 16.
Ferritins are iron storage proteins that overcome the problems of toxicity and poor bioavailability of iron by catalyzing iron oxidation and mineralization through the activity of a diiron ferroxidase site. Unlike in other ferritins, the oxidized di-Fe site of Escherichia coli bacterioferritin (EcBFR) is stable and therefore does not function as a conduit for the transfer of Fe into the storage cavity, but instead acts as a true catalytic cofactor that cycles its oxidation state while driving Fe oxidation in the cavity. Herein, we demonstrate that EcBFR mineralization depends on three aromatic residues near the diiron site, Tyr25, Tyr58, and Trp133, and that a transient radical is formed on Tyr25. The data indicate that the aromatic residues, together with a previously identified inner surface iron site, promote mineralization by ensuring the simultaneous delivery of two electrons, derived from Fe oxidation in the BFR cavity, to the di-ferric catalytic site for safe reduction of O.
铁蛋白是铁储存蛋白，通过二价铁氧化酶位点的活性催化铁氧化和矿化，克服了铁的毒性和生物利用度差的问题。与其他铁蛋白不同，大肠杆菌细菌铁蛋白（EcBFR）的氧化二价铁位点是稳定的，因此不作为铁转移到储存腔的通道，而是作为一个真正的催化辅因子，在驱动腔内铁氧化的同时循环其氧化态。在此，我们证明EcBFR矿化取决于二价铁位点附近的三个芳香族残基，即Tyr25、Tyr58和Trp133，并且在Tyr25上形成了一个瞬态自由基。数据表明，这些芳香族残基与先前确定的内表面铁位点一起，通过确保将两个电子（源自BFR腔内的铁氧化）同时传递到二价铁催化位点以安全还原O，从而促进矿化。
