在结构指导下发现新的脱氨酶酶
Daniel S Hitchcock1, Hao Fan, Jungwook Kim
1Department of Biochemistry & Biophysics and ‡Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
Journal of the American Chemical Society
|August 24, 2013
概括
这项研究使用结构导向方法来识别和表征胺酸酶超级家族中具有未知的功能的酶. 研究人员发现了新的酶活动,包括各种腺类别的去胺和受损的腺形式的去胺,帮助蛋白质注释.
科学领域:
- 基因组酶学 是一种基因组酶学.
- 蛋白质的生物化学 蛋白质的生物化学
- 结构生物学是结构生物学.
背景情况:
- 具有未知功能的蛋白质的可靠注释在基因组酶学中是一个重大挑战.
- 氨基氨酸酶超级家族包含许多具有未表征功能的酶.
- 之前的工作确定了Tm0936作为一种酶,可以去除S-adenosylhomocysteine (SAH) 的氨基酸.
研究的目的:
- 采用结构导向方法,对来自阿米多酶超级家族的未经表征的酶进行调查.
- 为了确定这个蛋白质家族中的新型酶活性和基质特异性.
- 为了改善功能不明的蛋白质的功能注释.
主要方法:
- 生物信息学,计算生物学和分子酶学的整合.
- 结构导向分析,包括分子对接和X射线晶体学.
- 对15种候选蛋白质进行净化和酶分析.
主要成果:
- 识别了能够去氨基化各种腺类别 (SAH,MTA,Ado,5'-dAdo) 的酶子组.
- 发现了第一个能够去除5'-deoxyadenosine (5'-dAdo) 的酶 (Dvu1825).
- 具有新型活动的特征酶,包括关氨酸去胺和氧化腺素形式 (2-oxoadenine,8-oxoadenine) 的去胺.
结论:
- 一种多学科的,结构导向的方法对于注释功能未知的酶是有效的.
- 这项研究扩展了已知的amidohydrolase超级家族的功能表.
- 为834个蛋白质序列提出了基底资料,增强了基因组注释.
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