Lipopeptide substrates for SpsB, the Staphylococcus aureus type I signal peptidase:: design, conformation and conversion to α-ketoamide inhibitors
Lipopeptide substrates for SpsB, the Staphylococcus aureus type I signal peptidase:: design, conformation and conversion to α-ketoamide inhibitors
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DOI：
10.1016/s0223-5234(03)00040-0
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发表时间：
2003-04-01
影响因子：
6.7
通讯作者：
Wang, L
中科院分区：
文献类型：
--
作者：
Bruton, G;Huxley, A;Wang, L
前蛋白序列数据用于设计SpsB（来自金黄色葡萄球菌的细菌信号肽酶I酶）的底物。金黄色。关键元素是烷基膜锚，P5处的脯氨酸和P2处的赖氨酸。P5处的脯氨酸诱导脂肽的螺旋转向。如从NMR研究推断的，在膜模拟溶剂中从P6到P2。如预期的，底物癸酰基-LTPTKAASKIDD-OH被SpsB在Pl和Pl'丙氨酸之间裂解，在pH 8.5下k（cat）/K-m为2.3 x 10（6）M-1 s（-1）。在P1'处插入脯氨酸将底物转化为竞争性抑制剂，而在裂解位点处掺入α-酮酰胺将底物转化为SpsB的时间依赖性抑制剂。(C)2003年，Elsevier SAS科学与医学版。All rights reserved.
Pre-protein sequence data was used to design substrates for SpsB, the bacterial signal peptidase I enzyme from Staphylococcus aureus. aureus. Key elements were an alkyl membrane anchor, proline at P5 and lysine at P2. The proline at P5 induced a helical turn in the lipopeptide. as deduced from NMR studies, from P6 to P2 in membrane mimetic solvents. The substrate Decanoyl-LTPTAKAASKIDD-OH was cleaved by SpsB, as expected, between the PI and Pl' alanines with a k(cat)/K-m of 2.3 x 10(6) M-1 s(-1) at pH 8.5. Insertion of proline at P1' converted substrates to competitive inhibitors, whilst the incorporation of an alpha-ketoamide at the cleavage site transformed substrates to time dependent inhibitors of SpsB. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.