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Function of your protein

The protein Ornithinine Aminotransferase (OAT), in humans (hOAT), is an enzyme that catalyzes the reaction between carbamoyl phosphate and orthinine to form citrulline and phosphate. Its ligand is pyridoxal-5'phosphate (PLP) which is a cofactor of the reaction. An amino group from L-Orn is transferred to PLP which turns it into pyridoxine phosphate (PMP) and L-Orn is converted to L glutamate-y-semialdehyde. PLP is regenerated when the amino group PMP is transferred to alpha-KG.

Biological relevance and broader implications

hOAT is an ubiquitous enzyme found in almost all organisms has been found to be overexpressed in hepatocellular carcinoma cells (HCC), which is a type of liver cancer. It is found predominantly in the liver and kidney. The liver, where it is an integral part of the urea cycle, and the intestine, where it synthesizes citrulline for export and plays a major role in amino acid homeostasis, particularly of L-glutamine and L-arginine.Studying this protein could be a potential drug to target cancer as a different therapy and radiation. hOAT has been a target mechanism-based inactivator (MBIs) in drug design efforts. HCC is diagnosed in advanced type of cancer which makes it more resistant to chemotherapy. hOAT inhibitors were created as fragmented-sized alternative substances such as GABA and 5-aminovaleric acid (AVA). hOAT was soaked with GABA and AVA and the new substrates prevented original interactions with catalytic amino acids and the ligand (PLP) which creates a tighter to hOAT instead of L-ornithine. GABA and AVA had stronger binding affinity and slower turnovers which makes them potential drug targets for hOAT.

Important amino acids

Amino Acids in PLP binding site are Lys 292, Asp 263, and Arg 180. They are essential to the active site. PLP is covalently bonded to the amino acid lysine. The phosphate group interacts with the positively charged nitrogen of the arginine side chain. There is also a pi-stacking interaction between its ring and the ring of PLP.

Structural highlights

hOAT is a protein with a secondary structure consisting of mainly alpha-helices but it also has parallel and anti-parallel beta-sheets and random coil. It's a polymer with a globular structure that has three subunits held together by non-covalent interactions such as hydrogen bonds and salt bridges hidden in the protein. The has a phosphate group surrounded by polar amino acids, carbons are surrounded by non-polar amino acids to satisfy the needs of the ligand and active site. Interactions like hydrogen bonding and pi-stacking stabilize and bind the ligand in the active site. This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.