“O-GlcNAc转移酶”(OGT)是哺乳动物的一种必要的酶，起营养物传感器的作用。它使带“O-linked β-N-acetylglucosamine (O-GlcNAc)”的蛋白发生糖基化，这种作用调控各种不同的细胞信号通道。Suzanne Walker及其同事介绍了人OGT与UDP形成的二元复合物的晶体结构以及与UDP和一个肽基质形成的三元复合物的晶体结构。这些结构显示了OGT是怎样识别肽序列的，也提供了关于在包括糖尿病、癌症和阿尔茨海默氏症等在内的若干人类疾病中以异常形式被发现的一种酶的作用机制的信息。（生物谷Bioon.com）
生物谷推荐原文出处：
Nature doi:10.1038/nature09638
Structure of human O-GlcNAc transferase and its complex with a peptide substrate
Michael B. Lazarus,Yunsun Nam,Jiaoyang Jiang,Piotr Sliz& Suzanne Walker
The essential mammalian enzyme O-linked β-N-acetylglucosamine transferase (O-GlcNAc transferase, here OGT) couples metabolic status to the regulation of a wide variety of cellular signalling pathways by acting as a nutrient sensor1. OGT catalyses the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine (UDP-GlcNAc) to serines and threonines of cytoplasmic, nuclear and mitochondrial proteins2, 3, including numerous transcription factors4, tumour suppressors, kinases5, phosphatases1 and histone-modifying proteins6. Aberrant glycosylation by OGT has been linked to insulin resistance7, diabetic complications8, cancer9 and neurodegenerative diseases including Alzheimer’s10. Despite the importance of OGT, the details of how it recognizes and glycosylates its protein substrates are largely unknown. We report here two crystal structures of human OGT, as a binary complex with UDP (2.8?? resolution) and as a ternary complex with UDP and a peptide substrate (1.95??). The structures provide clues to the enzyme mechanism, show how OGT recognizes target peptide sequences, and reveal the fold of the unique domain between the two halves of the catalytic region. This information will accelerate the rational design of biological experiments to investigate OGT’s functions; it will also help the design of inhibitors for use as cellular probes and help to assess its potential as a therapeutic target.
