Department of Chemistry, Texas A&M University, College Station, Texas 77843-3012, USA.
Protein Sci. 2011 Dec;20(12):2080-94. doi: 10.1002/pro.748. Epub 2011 Nov 9.
Adenine deaminase (ADE) from the amidohydrolase superfamily (AHS) of enzymes catalyzes the conversion of adenine to hypoxanthine and ammonia. Enzyme isolated from Escherichia coli was largely inactive toward the deamination of adenine. Molecular weight determinations by mass spectrometry provided evidence that multiple histidine and methionine residues were oxygenated. When iron was sequestered with a metal chelator and the growth medium supplemented with Mn(2+) before induction, the post-translational modifications disappeared. Enzyme expressed and purified under these conditions was substantially more active for adenine deamination. Apo-enzyme was prepared and reconstituted with two equivalents of FeSO(4). Inductively coupled plasma mass spectrometry and Mössbauer spectroscopy demonstrated that this protein contained two high-spin ferrous ions per monomer of ADE. In addition to the adenine deaminase activity, [Fe(II) /Fe(II) ]-ADE catalyzed the conversion of H(2)O(2) to O(2) and H(2)O. The values of k(cat) and k(cat)/K(m) for the catalase activity are 200 s(-1) and 2.4 × 10(4) M(-1) s(-1), respectively. [Fe(II)/Fe(II)]-ADE underwent more than 100 turnovers with H(2)O(2) before the enzyme was inactivated due to oxygenation of histidine residues critical for metal binding. The iron in the inactive enzyme was high-spin ferric with g(ave) = 4.3 EPR signal and no evidence of anti-ferromagnetic spin-coupling. A model is proposed for the disproportionation of H(2)O(2) by [Fe(II)/Fe(II)]-ADE that involves the cycling of the binuclear metal center between the di-ferric and di-ferrous oxidation states. Oxygenation of active site residues occurs via release of hydroxyl radicals. These findings represent the first report of redox reaction catalysis by any member of the AHS.
腺嘌呤脱氨酶(ADE)属于酰胺水解酶超家族(AHS)的酶,可催化腺嘌呤转化为次黄嘌呤和氨。从大肠杆菌中分离得到的酶对腺嘌呤的脱氨作用几乎没有活性。质谱法测定分子量的结果表明,多个组氨酸和蛋氨酸残基被氧化。在用金属螯合剂螯合铁并在诱导前用锰(2+)补充生长培养基的情况下,这些翻译后修饰消失了。在这些条件下表达和纯化的酶对腺嘌呤脱氨作用的活性大大提高。制备并与两当量的 FeSO 4 重组酶的无金属辅基形式。电感耦合等离子体质谱和穆斯堡尔光谱表明,这种蛋白质每个 ADE 单体含有两个高自旋亚铁离子。除了腺嘌呤脱氨酶活性外,[Fe(II)/Fe(II)]-ADE 还能催化 H 2 O 2 转化为 O 2 和 H 2 O。该酶的过氧化氢酶活性的 k cat 和 k cat / K m 值分别为 200 s -1 和 2.4×10 4 M -1 s -1 。由于对金属结合至关重要的组氨酸残基的氧化,[Fe(II)/Fe(II)]-ADE 在失活之前可与 H 2 O 2 进行超过 100 次周转。失活酶中的铁为高自旋三价铁,g 平均值为 4.3,没有反铁磁自旋偶合的证据。提出了一个模型,用于解释[Fe(II)/Fe(II)]-ADE 歧化 H 2 O 2 的反应,该模型涉及双核金属中心在二铁和二亚铁氧化态之间循环。活性位点残基的氧化通过释放羟自由基发生。这些发现代表了 AHS 中任何成员的氧化还原反应催化的首次报道。