Vath G M, Earhart C A, Rago J V, Kim M H, Bohach G A, Schlievert P M, Ohlendorf D H
Department of Biochemistry, University of Minnesota Medical School, Minneapolis 55455, USA.
Biochemistry. 1997 Feb 18;36(7):1559-66. doi: 10.1021/bi962614f.
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.
剥脱毒素A（ETA）可引发葡萄球菌烫伤样皮肤综合征，其特征为皮肤各层出现特定的表皮内分离。尽管有人认为蛋白酶或超抗原活性与之有关，但ETA导致皮肤分离的机制尚不清楚。ETA的X射线晶体结构已通过两种晶体形式解析出来，分辨率分别为2.1 Å和2.3 Å，R因子分别为17%和19%。这些结构表明ETA属于丝氨酸蛋白酶的胰凝乳蛋白酶样家族，在酸性残基后切割底物。有人认为，与催化位点相邻的一个环的构象通过控制Pro192的主链羰基是否占据氧阴离子孔，在调节ETA的蛋白水解活性方面起关键作用。一个独特的氨基末端结构域含有一个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会消除ETA产生表皮层特征性分离的能力，但不会消除其诱导T细胞增殖的能力。
