Substrate specificity provides insights into the sugar donor recognition mechanism of O-GlcNAc transferase (OGT).

O-Linked β-N-acetylglucosaminyl transferase (OGT) plays an important role in the glycosylation of proteins, which is involved in various cellular events. In human, three isoforms of OGT (short OGT [sOGT]; mitochondrial OGT [mOGT]; and nucleocytoplasmic OGT [ncOGT]) share the same catalytic domain, implying that they might adopt a similar catalytic mechanism, including sugar donor recognition. In this work, the sugar-nucleotide tolerance of sOGT was investigated. Among a series of uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc) analogs tested using the casein kinase II (CKII) peptide as the sugar acceptor, four compounds could be used by sOGT, including UDP-6-deoxy-GlcNAc, UDP-GlcNPr, UDP-6-deoxy-GalNAc and UDP-4-deoxy-GlcNAc. Determined values of Km showed that the substitution of the N-acyl group, deoxy modification of C6/C4-OH or epimerization of C4-OH of the GlcNAc in UDP-GlcNAc decreased its affinity to sOGT. A molecular docking study combined with site-directed mutagenesis indicated that the backbone carbonyl oxygen of Leu653 and the hydroxyl group of Thr560 in sOGT contributed to the recognition of the sugar moiety via hydrogen bonds. The close vicinity between Met501 and the N-acyl group of GlcNPr, as well as the hydrophobic environment near Met501, were responsible for the selective binding of UDP-GlcNPr. These findings illustrate the interaction of OGT and sugar nucleotide donor, providing insights into the OGT catalytic mechanism

Alibaba's strategic drift

It is fundamental in both a theoretical and practical sense, to analyse the strategies of successful e-businesses who were formulated and operated alongside incumbent competitors. Thus, there have been an array of strategic arguments concerning the rapidly-burgeoning virtual powerhouse Alibaba, who amidst a sea of fortified competitors, found their ground to become one of the most prominent e-businesses of the decade. At the commencing stages, Alibaba lacked a specific strategic goal, aside from the ethnic-originated ecology scheme. Further mishaps arose even after the take-off stage, when Alibaba opted to adhere to the diversification strategy, an evidently unusual phase for a virtual firm. Hence, it is the subject of common debate as to whether Alibaba cited a definitive strategic goal which guided their progress, or whether they were merely the product of a breakneck growth in the Chinese economy. This research will show how a leading e-Commerce company Alibaba has built B2B/C2C business portal Taobao/TMall and has transformed its transaction system from zhifubao into yuerbao and how it propelled Alipay to become a leading financial institution in the thriving digital market. In addition, strategic diversification on Chinese digital business will be examined through Alibaba case