催化部位近距离剖析,以实现不同序列的激素S-Adenosylmethionine酶的功能统一
Timothy W Precord1,2, Sangeetha Ramesh3,2, Shravan R Dommaraju1,2
1Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
ACS bio & med chem Au
|June 26, 2023
概括
使用"催化位点接近"的新方法准确预测了参与RiPP生物合成的激进S-adenosylmethionine (rSAM) 酶的功能. 这种方法可以识别出新型的sactipeptide组,并增强蛋白质的功能注释.
科学领域:
- 生物化学和分子生物学
- 酶学 是一种酶学.
- 生物信息学是一种生物信息学.
背景情况:
- 激进的S-adenosylmethionine (rSAM) 超级家族是新型酶化学的丰富来源,特别是在核糖体合成和翻译后修饰 (RiPPs) 的生物合成中.
- 尽管生物信息学取得了进展,但对大量已识别的rSAM蛋白质的功能进行准确的注释仍然是一个重大挑战.
研究的目的:
- 开发和验证一种用于预测参与RiPP生物合成的rSAM蛋白的功能的新方法.
- 通过开发的预测方法,识别新类的sactipeptides.
主要方法:
- 创建了约15,000个参与RiPP生物合成的高可靠性rSAM蛋白的汇编.
- 序列分析和蛋白质结构预测,以确定"催化位点附近"残留物.
- 实验验证使用质谱,向突变发生和化学降解在一个案例研究酶 (StsB).
主要成果:
- 识别具有强大的功能预测能力的"催化位点附近"残留物,对rSAM酶,特别是形成sactionine链接的酶.
- 实验证实,最初与MftC相似的*Streptomyces sparsogenes*中的StsB,正如新方法预测的那样,形成了sactionine键.
- 发现了六个新的sactipeptide组,以前无法通过传统的基因组挖掘策略检测到.
结论:
- "催化位点近距离"分析是一种强大的工具,可以增强和纠正rSAM蛋白的功能预测.
- 这种方法显著扩大了在rSAM超级家族内的新型RiPP和酶功能的发现潜力.
- 该方法显示了广泛的适用性,包括对旋形成的rSAM蛋白质,有望在酶学和基因组学中产生更广泛的影响.
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