Mutations in X-linked ichthyosis disrupt the active site structure of estrone/DHEA sulfatase
Mutations in X-linked ichthyosis disrupt the active site structure of estrone/DHEA sulfatase
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DOI：
10.1016/j.bbadis.2004.09.003
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发表时间：
2004-12-24
影响因子：
6.2
通讯作者：
Ghosh, D
中科院分区：
文献类型：
--
作者：
Ghosh, D
X连锁鱼鳞病是一种遗传性皮肤病，由于类固醇硫酸酯酶（STS）缺乏。先前已报道STS基因的7个关键点突变，6个导致氨基酸取代，1个导致多肽链提前终止。最近已经确定了全长人类酶的三维结构。由于X连锁鱼鳞病中的点突变而引起的氨基酸取代被映射到人类STS的三维结构上。在每种情况下，取代似乎会导致破坏的活性位点的架构或干扰酶的推定膜相关的图案的催化裂缝的完整性至关重要，从而提供了一个解释STS活性的损失。(C)2004 Elsevier B.V保留所有权利。
X-linked ichthyosis is an inherited genetic disorder of the skin that results from steroid sulfatase (STS) deficiency. Seven critical point mutations have been previously reported for the STS gene, six leading to amino acid substitutions and one to a premature termination of the polypeptide chain. The three-dimensional structure of the full-length human enzyme has been recently determined. Amino acid substitutions due to point mutations in X-linked ichthyosis are mapped onto the three-dimensional structure of human STS. In each case, the substitution appears to cause disruption of the active site architecture or to interfere with the enzyme's putative membrane-associating motifs crucial to the integrity of the catalytic cleft, thereby providing an explanation for the loss of STS activity. (C) 2004 Elsevier B.V All rights reserved.