探索GrsB硫酶的基质灵活性导致了格拉米西丁S变体的结构重新分配
Sho Konno1, Tomoe Mizuguchi1, Atsuko Suzuki1
1School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
Chembiochem : a European journal of chemical biology
|July 2, 2025
概括
研究人员研究了酶格拉米西丁S合成酶B (GrsB) 如何处理改性前体. 他们在铁酶 (TE) 域中发现了意想不到的立体化学灵活性,修改了Gramicidin S (GS) 变体的结构.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 酶学 是一种酶学.
背景情况:
- 格拉米西丁S (GS) 是一种由格拉米西丁S合成酶B (GrsB) 合成的循环解.
- GrsB的C-终端化酶 (TE) 域对于五前体的二度化和十的循环化至关重要.
- 此前曾报道过一种修改后的GS变体 (GS-SA),其中L-Ser(Allyl) 取代了D-Phe.
研究的目的:
- 为了研究GrsB TE域的基质特异性.
- 了解含有L-Ser(Allyl) 的改性前体的加工过程.
- 为了澄清报告的GS-SA变异的结构.
主要方法:
- 使用合成线性的酶循环化试验.
- 高性能液态色谱 (HPLC) 用于分析合成产品.
- 结构和功能分析包括1H核磁共振 (NMR),抗微生物测定和循环二元化 (CD) 光谱.
主要成果:
- GrsB-TE成功地在6位循环L-Ser(Allyl) 的基质,但在1位却没有.
- 与报告的变种相比,酶合成的GS-SA表现出不同的HPLC保留时间.
- 结构分析显示,报告的GS-SA变种实际上含有D-Ser(Allyl),而不是L-Ser(Allyl).
结论:
- GrsB TE域显示出以前未被认可的立体化学灵活性.
- 这些发现需要对先前报告的GS-SA变异进行结构性修订.
- 这项研究为改性基质的酶处理提供了新的见解.
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