What is the function of OGT?

What is the function of OGT?

OGT is involved in the resistance of insulin in muscle cells and adipocytes by inhibiting the Threonine 308 phosphorylation of AKT1, increasing the rate of IRS1 phosphorylation (at serine 307 and serine 632/635), reducing insulin signaling, and glycosylating components of insulin signals.

What does GlcNAc do?

As UDP-GlcNAc is the final product of the hexosamine biosynthetic pathway, which integrates amino acid, carbohydrate, fatty acid, and nucleotide metabolism, it has been suggested that O-GlcNAc acts as a “nutrient sensor” and responds to the cell’s metabolic status.

How does Thiamet G work?

Thiamet G is a potent, selective O-GlcNAcase inhibitor with Kiof 21 nM, while exhibiting 37,000-fold selectivity over human lysosomal –hexosaminidase. In O-GlcNAc transferase or O-GlcNAcase gain of function cells, thiamet-G restores the assembly of the spindle and partially rescues histone phosphorylation.

Why do proteins get glycosylated?

Protein glycosylation helps in proper folding of proteins, stability and in cell to cell adhesion commonly needed by cells of the immune system. The major sites of protein glycosylation in the body are ER, Golgi body, nucleus and the cell fluid.

How do you pronounce GlcNAc?

Building on their previous research, which showed how an abundant but difficult-to-detect sugar switch known as O-GlcNAc (pronounced oh-GLICK-nack) responded to nutrients and stress, the Hopkins team knew this small molecule was elevated in the red cells of patients with diabetes.

Is O-GlcNAc a glycan?

O-GlcNAc is distinct from all other common forms of protein glycosylation in several major respects (Figure 18.1). A long-held dogma, still promulgated in many cell biology and biochemistry textbooks today, is that protein glycosylation does not occur within the cytoplasmic and nuclear compartments of the cell.

What does GlcNAc stand for?

N-Acetylglucosamine (GlcNAc) is an amide derivative of the monosaccharide glucose. It is a secondary amide between glucosamine and acetic acid. It is significant in several biological systems.

What is OGA in biology?

1.169, OGA, glycoside hydrolase O-GlcNAcase, O-GlcNAcase, BtGH84, O-GlcNAc hydrolase) is an enzyme with systematic name (protein)-3-O-(N-acetyl-D-glucosaminyl)-L-serine/threonine N-acetylglucosaminyl hydrolase. OGA is encoded by the MGEA5 gene.

What types of proteins are glycosylated?

Glycosylated proteins (glycoproteins) are found in almost all living organisms that have been studied, including eukaryotes, eubacteria and archae (3,4). Eukaryotes have the greatest range of organisms that express glycoproteins, from single-celled to complex multicellular organisms.

Where do glycosylated proteins go?

Glycosylation of proteins and lipids occurs in the endoplasmic reticulum (ER) and Golgi apparatus, with most of the terminal processing occurring in the cis-, medial- and trans-Golgi compartments.

Is N-acetylglucosamine a protein?

UDP -N-acetylglucosamine: α-3-D-mannoside β-1,2-N-acetylglucosaminyl transferase I (G1cNac-TI) is a key enzyme in N-linked protein glycosylation. It is encode by a single gene termed Mgat in mouse.

Is N-acetylglucosamine a sugar?

N-acetylglucosamine (also known as N-acetyl glucosamine) is a simple sugar derived from the outer shell of crustaceans.

What is O-GlcNAc transferase?

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 sensor 1.

How does glycosyltransferase OGT detect glucose?

In eukaryotes, a major mechanism for nutrient sensing involves the essential 11 protein glycosyltransferase OGT, which senses cellular glucose levels via UDP-GlcNAc concentrations, and responds by dynamically O -GlcNAcylating a wide range of nuclear and cytoplasmic proteins 1, 12.

Why is OGT so important in metazoan biology?

It is the only known metazoan glycosyltransferase that glycosylates proteins in the cytoplasm and nucleus, and its importance is metazoan biology is indisputable. What is less clear is why it is so important. What does OGT do for mammalian cells that makes it essential?

Are there any structures of OGT that we have solved?

We have solved numerous structures of OGT with substrates, substrate analogs, inhibitors, and products bound, with more to come. Michael Lazarus et al.” Structure of human O-GlcNAc transferase and its complex with a peptide substrate,” Nature 2011, 469:564-567 (PDB codes: 3PE3, 3PE4)