通过一种新的机制在不和葡萄基酸酶中进行糖酸裂解
Seino A K Jongkees1, Stephen G Withers
1Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, Canada V6T 1Z1.
Journal of the American Chemical Society
|November 4, 2011
概括
不和基酸盐 (UGLs) 使用一种新的乙烯基乙烯水化机制进行糖键裂解,与经典酸盐不同. 这条在细菌感染中至关重要的途径提供了新的治疗点.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 葡萄糖生物学 葡萄糖生物学
背景情况:
- 不和葡萄基酸酶 (UGLs) 是糖化酸酸酶 (GH) 88.家族中的酶.
- 它们从细菌多糖酸酶产生的寡糖酸中分离出不和糖.
- 这一过程在细胞外细菌感染中至关重要,并且没有哺乳动物对应物.
研究的目的:
- 为拟议的UGL行动的新机制提供明确的证据.
- 调查UGL的催化机制,特别是拟议的乙烯基以太水化途径.
- 为了区分UGL机制与经典的酶机制.
主要方法:
- 在H2O,D2O和稀释甲醇/水中UGL催化反应的产品分析.
- 测试UGL在硫糖化物和反转异构构的糖化物上的活性.
- 评估C-糖类同类物体的UGL催化化.
- 测量β-二次运动同位素效应.
主要成果:
- UGL被证明可催化乙烯基乙烯基组的水合,从而导致甘氨基酸键裂变.
- 耐古典葡萄糖酶的基质,如硫糖酸,被UGLs快速切割.
- 一种C-葡萄糖类类似物经过了水化,支持了水化启动的机制.
- 一个小的β-二次动态同位素效应表明了氧碳离子过渡状态.
结论:
- 这项研究验证了一种用于UGLs的新乙烯乙烯水化机制.
- 这种机制不同于在异构碳上逆转或保留直接酶机制.
- 这些发现提供了对UGL在细菌病变发生过程中的作用的更深入理解.
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