Structural similarities and differences in staphylococcus aureus exfoliative toxins A and B as revealed by their crystal structures
Structural similarities and differences in staphylococcus aureus exfoliative toxins A and B as revealed by their crystal structures
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DOI：
10.1110/ps.9.3.610
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发表时间：
2008-12
期刊：
影响因子：
8
通讯作者：
A. Papageorgiou;K. Acharya;L. Plano;C. Collins
中科院分区：
文献类型：
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作者：
A. Papageorgiou;K. Acharya;L. Plano;C. Collins
金黄色葡萄球菌表皮毒素A和B是引起新生儿和幼儿烫伤样皮肤综合征的原因。这种综合征的临床特征从局部水疱到严重的表皮剥脱，影响大部分身体表面。比较两种亚型的rETA（2.0 nm分辨率），rETB（2.8 nm分辨率）和rETA的活性位点变体Ser 195 Ala（2.0 nm分辨率）的晶体结构，表明它们的整体拓扑结构类似于“胰蛋白酶样”丝氨酸蛋白酶，但在N-和C-末端和环区域有显着差异。两种ET结构中的催化位点的细节与谷氨酸特异性丝氨酸蛋白酶中的催化位点非常相似，表明了共同的催化机制。然而，作为谷氨酸特异性丝氨酸蛋白酶的催化位点的一部分的“氧阴离子空穴”对于rETA处于闭合或非活性构象，而对于rETB处于开放或活性构象。在N-末端含有独特的两亲性螺旋，并且它似乎参与优化催化位点残基的构象。的rETA催化位点的变体，Ser 195 Ala的结构的测定，显示在活性位点没有显着的扰动，建立的生物和酯水解活性的损失可以完全归因于破坏的催化丝氨酸残基。最后，丝氨酸蛋白酶的晶体结构，以及生物化学数据和诱变研究，强烈证实了这些分子的分类为“丝氨酸蛋白酶”，而不是“超抗原”。
Staphylococcal aureus epidermolytic toxins (ETs) A and B are responsible for the induction of staphylococcal scalded skin syndrome, a disease of neonates and young children. The clinical features of this syndrome vary from localized blisters to severe exfoliation affecting most of the body surface. Comparison of the crystal structures of two subtypes of ETs‐rETA (at 2.0 Å resolution), rETB (at 2.8 Å resolution), and an active site variant of rETA, Ser195Ala at 2.0 Å resolution has demonstrated that their overall topology resembles that of a “trypsin‐like” serine protease, but with significant differences at the N‐ and C‐termini and loop regions. The details of the catalytic site in both ET structures are very similar to those in glutamate‐specific serine proteases, suggesting a common catalytic mechanism. However, the “oxyanion hole,” which is part of the catalytic sites of glutamate specific serine proteases, is in the closed or inactive conformation for rETA, yet in the open or active conformation for rETB. The ETs contain a unique amphipathic helix at the N‐terminus, and it appears to be involved in optimizing the conformation of the catalytic site residues. Determination of the structure of the rETA catalytic site variant, Ser195Ala, showed no significant perturbation at the active site, establishing that the loss of biological and esterolytic activity can be attributed solely to disruption of the catalytic serine residue. Finally, the crystal structure of ETs, together with biochemical data and mutagenesis studies, strongly confirms the classification of these molecules as “serine proteases” rather than “superantigens.”