The structure of the superantigen exfoliative toxin A suggests a novel regulation as a serine protease.
The structure of the superantigen exfoliative toxin A suggests a novel regulation as a serine protease.
复制标题
DOI：
10.1021/bi962614f
复制
发表时间：
1997-02
期刊：
影响因子：
2.9
通讯作者：
G. M. Vath;C. A. Earhart;J. Rago;Michael H. Kim;G. Bohach;P. Schlievert;D. Ohlendorf
中科院分区：
文献类型：
--
作者：
G. M. Vath;C. A. Earhart;J. Rago;Michael H. Kim;G. Bohach;P. Schlievert;D. Ohlendorf
剥脱毒素A （ETA）引起葡萄球菌性烫伤皮肤综合征，其特征是皮肤层的特异性表皮内分离。ETA引起皮肤分离的机制尚不清楚，尽管蛋白酶或超抗原活性已被涉及。ETA的x射线晶体结构以2.1和2.3 A的分辨率和17%和19%的r因子解算为两种晶型。结构表明ETA属于凝乳胰蛋白酶样丝氨酸蛋白酶家族，并在酸残基后切割底物。邻近催化位点的环构象被认为是通过控制Pro192主链羰基是否占据氧阴离子空穴来调节ETA蛋白水解活性的关键。一个独特的氨基末端结构域含有15个残基的两亲性α螺旋，也可能通过结合特定受体参与蛋白酶激活。用半胱氨酸取代活性位点丝氨酸残基可消除ETA产生表皮层特征分离的能力，但不会消除其诱导T细胞增殖的能力。
Exfoliative toxin A (ETA) causes staphylococcal scalded skin syndrome which is characterized by a specific intraepidermal separation of layers of the skin. The mechanism by which ETA causes skin separation is unknown although protease or superantigen activity has been implicated. The X-ray crystal structure of ETA has been solved in two crystal forms to 2.1 and 2.3 A resolution and R-factors of 17% and 19%, respectively. The structures indicate that ETA belongs to the chymotrypsin-like family of serine proteases and cleaves substrates after acidic residues. The conformation of a loop adjacent to the catalytic site is suggested to be key in regulating the proteolytic activity of ETA through controlling whether the main chain carbonyl group of Pro192 occupies the oxyanion hole. A unique amino-terminal domain containing a 15-residue amphipathic alpha helix may also be involved in protease activation through binding a specific receptor. Substitution of the active site serine residue with cysteine abolishes the ability of ETA to produce the characteristic separation of epidermal layers but not its ability to induce T cell proliferation.