“O-GlcNAc轉(zhuǎn)移酶”(OGT)是哺乳動(dòng)物的一種必要的酶,，起營養(yǎng)物傳感器的作用。它使帶“O-linked β-N-acetylglucosamine (O-GlcNAc)”的蛋白發(fā)生糖基化,，這種作用調(diào)控各種不同的細(xì)胞信號通道,。Suzanne Walker及其同事介紹了人OGT與UDP形成的二元復(fù)合物的晶體結(jié)構(gòu)以及與UDP和一個(gè)肽基質(zhì)形成的三元復(fù)合物的晶體結(jié)構(gòu)。這些結(jié)構(gòu)顯示了OGT是怎樣識別肽序列的,，也提供了關(guān)于在包括糖尿病,、癌癥和阿爾茨海默氏癥等在內(nèi)的若干人類疾病中以異常形式被發(fā)現(xiàn)的一種酶的作用機(jī)制的信息。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
