von Figura K, Schmidt B, Selmer T, Dierks T
Georg-August-Universität, Abt Biochemie II, Göttingen, Germany.
Bioessays. 1998 Jun;20(6):505-10. doi: 10.1002/(SICI)1521-1878(199806)20:6<505::AID-BIES9>3.0.CO;2-K.
In multiple sulfatase deficiency, a rare human lysosomal storage disorder, all known sulfatases are synthesized as catalytically poorly active polypeptides. Analysis of the latter has shown that they lack a protein modification that was detected in all members of the sulfatase family. This novel protein modification generates a 2-amino-3-oxopropanoic acid (C alpha-formylglycine) residue by oxidation of the thiol group of a cysteine that is conserved among all eukaryotic sulfatases. The oxidation occurs in the endoplasmic reticulum at a stage when the nascent polypeptide is not yet folded. The aldehyde is part of the catalytic site and is likely to act as an aldehyde hydrate. One of the geminal hydroxyl groups accepts the sulfate during sulfate ester cleavage leading to the formation of a covalently sulfated enzyme intermediate. The other hydroxyl is required for the subsequent elimination of the sulfate and regeneration of the aldehyde group. In some prokaryotic members of the sulfatase gene family, the DNA sequence predicts a serine residue, and not a cysteine. Analysis of one of these prokaryotic sulfatases, however, revealed the presence of the C alpha-formylglycine indicating that the aldehyde group is essential for all members of the sulfatase family and that it can be generated from either cysteine or serine.
在多种硫酸酯酶缺乏症（一种罕见的人类溶酶体贮积症）中，所有已知的硫酸酯酶均以催化活性较差的多肽形式合成。对后者的分析表明，它们缺乏在硫酸酯酶家族所有成员中都检测到的一种蛋白质修饰。这种新的蛋白质修饰通过氧化所有真核生物硫酸酯酶中保守的半胱氨酸的巯基，产生一个2-氨基-3-氧代丙酸（Cα-甲酰甘氨酸）残基。氧化发生在内质网中新生多肽尚未折叠的阶段。醛基是催化位点的一部分，可能以醛水合物的形式起作用。在硫酸酯裂解过程中，其中一个偕羟基接受硫酸根，导致形成共价硫酸化的酶中间体。另一个羟基是随后消除硫酸根并使醛基再生所必需的。在硫酸酯酶基因家族的一些原核生物成员中，DNA序列预测的是丝氨酸残基，而非半胱氨酸。然而，对其中一种原核生物硫酸酯酶的分析显示存在Cα-甲酰甘氨酸，这表明醛基对硫酸酯酶家族的所有成员都是必不可少的，并且它可以由半胱氨酸或丝氨酸生成。
