Sandbox Reserved 1755
From Proteopedia
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| - | + | {{Sandbox_Reserved_BHall_F22}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | |
| - | ==(hOAT | + | ==Human Ornithinine Aminotransferase (hOAT)== |
<StructureSection load='7T9Z' size='340' side='right' caption='Caption for this structure' scene=''> | <StructureSection load='7T9Z' size='340' side='right' caption='Caption for this structure' scene=''> | ||
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs. | This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs. | ||
| - | You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID: | + | You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue. |
| - | == Function of your protein == catalyzes the | + | |
| + | ==(hOAT')== | ||
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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. It has 3 ligands pyridoxal-5' phosphate (PLP) which is a cofactor in the reaction. An amino group from L-Ornithinine is transferred to PLP which converts it to pyridoxamine phosphate (PMP) and L-Orn is converted to L-glutamate-y-semialdehyde. PLP is regenerated when PMP is transferred to alpha-KG. | ||
== Biological relevance and broader implications == | == Biological relevance and broader implications == | ||
| + | hOAT is a ubiquitous enzyme found in almost all organisms and 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 has diagnosed an 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 a stronger binding affinity and slower turnovers which makes them potential drug targets for hOAT. | ||
== Important amino acids== | == Important amino acids== | ||
<scene name='93/933999/Amino_acid_300-304/1'>Amino Acids 300-304</scene> are an important part of protein binding <ref>PMID:35460691</ref>. | <scene name='93/933999/Amino_acid_300-304/1'>Amino Acids 300-304</scene> are an important part of protein binding <ref>PMID:35460691</ref>. | ||
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== Structural highlights == | == Structural highlights == | ||
<scene name='93/933999/Helix/4'>An image of the helix in HOAT protein.</scene> | <scene name='93/933999/Helix/4'>An image of the helix in HOAT protein.</scene> | ||
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This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | ||
Current revision
| This Sandbox is Reserved from November 4, 2022 through January 1, 2023 for use in the course CHEM 351 Biochemistry taught by Bonnie Hall at the Grand View University, Des Moines, USA. This reservation includes Sandbox Reserved 1755 through Sandbox Reserved 1764. |
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Human Ornithinine Aminotransferase (hOAT)
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References
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
- ↑ Butrin A, Butrin A, Wawrzak Z, Moran G, Liu D. Determination of the pH-Dependence, Substrate Specificity and Turnovers of Alternative Substrates for Human Ornithine Aminotransferase. J Biol Chem. 2022 Apr 20:101969. doi: 10.1016/j.jbc.2022.101969. PMID:35460691 doi:http://dx.doi.org/10.1016/j.jbc.2022.101969
