Sandbox GGC8

GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase)

spinqualitylabelsall models GAPDH Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D GAPDH is a protein known as Glyceraldehyde-3-Phosphate dehydrogenase. This protein is also known as the "housekeeping" protein of the cell, it consists of an average of 335 amino acids, and it is considered a heme. It is also considered a catalyst to break down glucose to create energy and to form carbon molecules. It has many functions in the cell and is considered very important. This protein is mostly expressed in the most vital organs, the liver, brain, kidneys, and heart. Function This Particular Protein Plays a big role in Glycolysis and activities in the nucleus. Glyceraldehyde-3-phosphate dehydrogenase is a very important enzyme that catalyzes the first step of the glycolysis pathway. This is done by converting D-glyceraldehyde-3-phosphate to 3-phospho-D glyceroyl phosphate. The catalytic reaction begins with the reactants of D-glyceraldehyde-3-phosphate, NAD+, and phosphate. This reaction then proceeds with the products of (2R)-3- phospho-D glyceroyl phosphate, H ion, and NADH. This reaction then proceeds in the glycolysis pathway and creates pyruvate from D-glyceraldehyde-3-phosphate. Glyceraldehyde-3-Phosphate dehydrogenase has a big role in the nucleus. It is a part of many processes such as DNA replication, transcription, RNA transport, and apoptosis. Although it participates in all of those nuclear activities, it is mostly known to initiate apoptosis and transcription of the genes that are known to be involved in the antiapoptotic pathways and cell proliferation. GAPDH also plays a role in regulating of telomere length. Many biochemists have determined that this protein interacts with some types of DNA damages. Examples of them are apurinic/ apyrimidinic sites, nucleotide analogs, and covalent DNA adducts with alkylating agents. This then indicates and confirms that it participates in DNA repair by interacting with repair proteins such as APE1. This protein also plays a part in carbohydrate degradation. It catalyzes an energy-yielding step in carbohydrate metabolism. This happens when the nicotinamide adenine dinucleotide and the inorganic phosphate are present. This protein is a tetramer of chains that are identical. Regulation Glyceraldehyde-3-Phosphate dehydrogenase is regulated by being inhibited by Fumarate through the formation of S-(2-succinyl) cysteine residues. Disease GAPDH is expressed in many diseases and disorders. The main diseases and disorders that were confirmed from the expression of GAPDH are cancers and neurodegeneration. It has been confirmed that GAPDH is expressed in many cancers as its antiapoptotic function protects the tumor and cancerous cells in the body. The protection of those cells promotes tumorigeneses and their proliferation. GAPDH also protects against the shortening of telomeres. The shortening of telomeres is caused by chemotherapy. Furthermore, Oxidative Stress impairs protein function. By impairing GAPDH, it will cause the aging and the apoptosis of the cell. GAPDH can also manage to induce the biological aging of the cells which have been proved to maintain tumor growth and production. When paired with the right protein, GAPDH can be expressed in neurodegenerative diseases. The protein interaction with GAPDH can affect it functions such as energy metabolism, apoptosis, DNA replication, tRNA transport, and DNA repair. When the function of this Protein is affected, it could lead to disorders such as Parkinson’s disease and Huntington’s disease. Relevance This protein is a component in many reactions and helps the eukaryote function in many ways at the cellular level. If affected by protein interactions, it will have a big impact on the eukaryote especially in the vital organs of the animal or human as it plays a big role in the vital organs. It will also lose its function and can be fatal to the human body as its important functions are disturbed and disrupted. Structural highlights 1. protein interaction functional site 2. Disulfide Bridge interactions with SO4 3. NDP2 Interaction 4.Q-Protein Interactions

References

1. Tatton WG, Chalmers-Redman RM, Elstner M, Leesch W, Jagodzinski FB, Stupak DP, Sugrue MM, Tatton NA. Glyceraldehyde-3-phosphate dehydrogenase in neurodegeneration and apoptosis signaling. J Neural Transm Suppl. 2000;(60):77-100. doi: 10.1007/978-3-7091-6301-6_5. PMID: 11205159.

2. Carujo S, Estanyol JM, Ejarque A, Agell N, Bachs O, Pujol MJ. Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity. Oncogene. 2006 Jul 6;25(29):4033-42. doi: 10.1038/sj.onc.1209433. Epub 2006 Feb 13. PMID: 16474839.

3. Kosova, A.A., Khodyreva, S.N. & Lavrik, O.I. Role of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in DNA repair. Biochemistry Moscow 82, 643–654 (2017). https://doi.org/10.1134/S0006297917060013

4. Fermani S, Sparla F, Falini G, Martelli PL, Casadio R, Pupillo P, Ripamonti A, Trost P. Molecular mechanism of thioredoxin regulation in photosynthetic A2B2-glyceraldehyde-3-phosphate dehydrogenase. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11109-14. doi: 10.1073/pnas.0611636104. Epub 2007 Jun 15. PMID: 17573533; PMCID: PMC1904167.