Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
J Am Chem Soc. 2011 Aug 10;133(31):11826-9. doi: 10.1021/ja201179f. Epub 2011 Jul 15.
The pseudouridine synthase TruB handles 5-fluorouridine in RNA as a substrate, converting it into two isomeric hydrated products. Unexpectedly, the two products differ not in the hydrated pyrimidine ring but in the pentose ring, which is epimerized to arabinose in the minor product. This inversion of stereochemistry at C2' suggests that pseudouridine generation may proceed by a mechanism involving a glycal intermediate or that the previously proposed mechanism involving an acylal intermediate operates but with an added reaction manifold for 5-fluorouridine versus uridine. The arabino product strongly disfavors a mechanism involving a Michael addition to the pyrimidine ring.
假尿嘧啶核苷合成酶 TruB 将 5-氟尿嘧啶核苷作为底物用于 RNA 中，将其转化为两种异构的水合产物。出乎意料的是，这两种产物的区别不在于水合嘧啶环，而在于戊糖环，在次要产物中戊糖环被差向异构化为阿拉伯糖。C2'立体化学的这种反转表明，假尿嘧啶的生成可能通过涉及糖醛中间体的机制进行，或者先前提出的涉及酰基中间体的机制起作用，但对于 5-氟尿嘧啶与尿嘧啶，增加了一个反应途径。阿拉伯糖产物强烈反对涉及嘧啶环的迈克尔加成的机制。
