User:HHarach/Oxalate decarboxylase
| oxalate decarboxylase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Oxalate decarboxylase hexamer, Bacillus subtilis | |||||||||
| Identifiers | |||||||||
| EC no. | 4.1.1.2 | ||||||||
| CAS no. | 9024-97-9 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
Oxalate Decarboxylase
[edit]Oxalate decarboxylase (OxdC) (EC 4.1.1.2) [1] is an enzyme that can be found in a wide range of organisms and plays an important role in the metabolism of oxalates (oxalic acid). The EC number is the classification system used for enzymes and allows for the categorization of them based on their function. Breaking down the EC number of oxalate decarboxylase, it can be seen that it belongs to the lysase class, subclass carbon-carbon lysase, and sub-subclass carboxy lysase. It is responsible for the decarboxylation of oxalate, breaking it down into carbon dioxide and formate[2]. It appears in numerous biochemical pathways and is essential for preventing a buildup of oxalate, a potentially toxic chemical to various organisms[1].
Reaction Pathway
[edit]Oxalate decarboxylase catalyzes the following reaction:
oxalate + H+ ⇄ formate + CO2
This reaction also requires the presence of two cofactors: manganese (II) and dioxygen. However, it is not entirely known why they are necessary as cofactors. There are two manganese binding sites and it is believed that only one of the sites possesses catalytic activity while the other one is for structural purposes. Another interesting feature is the presence of molecular oxygen. Molecular oxygen is not a typical cofactor, but it is believed that it is present in oxalate decarboxylase to be an activator of the manganese center by increasing the molecule's redox potential even though there is no net redox change[1][3][4].
Organisms Found In
[edit]Oxalate decarboxylase can be found in a wide range of organisms including bacteria, fungi, and some plants. Some examples of these organisms include, but are not limited to:
Bacteria: Bacillus subtilis, Escherichia coli, Oxalobacter formigenes
Fungi: Aspergillus niger
Plants: Spinacia oleracea L. (spinach)[5]
All of these organisms possess oxalate decarboxylase to regulate oxalate levels or to use oxalates as a larger part of their metabolisms in some way. In either situation, the functionality of the enzyme is the same and that is to break down oxalates[6][7][8].
Role in Metabolism
[edit]The primary role in the metabolism of oxalate decarboxylase is in the breakdown of oxalates. Oxalates can build up in all of the organisms mentioned above and have a toxic effect when enough accumulates within the organism. With the help of oxalate decarboxylase, oxalates can be broken down and the formate and carbon dioxide can then be utilized for other parts of cellular/system metabolism or excreted. Formate specifically is especially useful for the metabolic pathways and can provide another source of one-carbon molecules for metabolism.[9]
Additionally, it is worth noting that humans do not naturally produce the oxalate decarboxylase enzyme. Instead, oxalate degradation by Oxalobacter formigenes is needed so that oxalates do not build up within the body. One key indicator of low levels of this bacteria is hyperoxaluria or an increased urinary excretion of oxalates. This is because the oxalates can not be broken down so they are just excreted as whole molecules. This then creates a different problem for humans since oxalates tend to bind to calcium. These calcium oxalates are one of the primary causes of kidney stones and will clump together to form hard, insoluble "stones" that will usually pass naturally over time through the urinary tract, but in some cases may need to be surgically removed[6][9][10].
Crystal Structures
[edit]
The overall structure of the oxalate decarboxylase enzyme was characterized using x-ray diffraction at varying resolutions since the initial analysis of it in 2002. This produced an overall total structural weight of 43.85 kDa and was primarily isolated from Bacillus subtilis bacteria. It is an overall hexamer with 32-point symmetry. It is also classified as a bicupin because it contains two copies of the cupin domain. Each oxalate decarboxylate cupin domain contains one manganese binding site[11][12].
Active Sites
[edit]Although it is not known for certain, it is hypothesized that the mutation of the alanine at position 333 of the amino acid chain in oxalate oxidase to glutamic acid in the oxalate decarboxylase is what allows the enzyme to act as a proton donor for the break down of oxalates to carbon dioxide and formate. Although dioxygen is necessary for the reaction to take place, the actual enzyme does not require the presence of oxygen based on reaction curves test in anaerobic environments. It is still dependent on manganese binding to remain active since it is a manganese-dependent enzyme[13].
The active site contains the manganese centers and has been identified as active under various studies. As previously mentioned, the structure of oxalate decarboxylase is extremely similar to oxalate oxidase with very few mutations that differentiate the two. With that being said, the active sites containing these metal ions are similar between the two and have allowed researchers to confirm the position of the active site in oxalate decarboxylase[14][13].
Structure and Function
[edit]Besides the function of breaking down oxalates, oxalate decarboxylase contains another metal binding site on its surface that has yet to be determined whether or not it has a functional value in the degradation of oxalates. This site may have another function in cells that contain this enzyme, but that has yet to be researched[14][13].
References
[edit]- ^ a b c "M-CSA Mechanism and Catalytic Site Atlas". www.ebi.ac.uk. Retrieved 2023-10-18.
- ^ "ExplorEnz: Contents". www.enzyme-database.org. Retrieved 2023-10-18.
- ^ Moomaw, Ellen W.; Angerhofer, Alexander; Moussatche, Patricia; Ozarowski, Andrew; García-Rubio, Inés; Richards, Nigel G. J. (2009-07-07). "Metal Dependence of Oxalate Decarboxylase Activity". Biochemistry. 48 (26): 6116–6125. doi:10.1021/bi801856k. ISSN 0006-2960. PMC 2801813. PMID 19473032.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Zhu, Wen; Easthon, Lindsey M.; Reinhardt, Laurie A.; Tu, Chingkuang; Cohen, Steven E.; Silverman, David N.; Allen, Karen N.; Richards, Nigel G. J. (2016-04-12). "Substrate Binding Mode and Molecular Basis of a Specificity Switch in Oxalate Decarboxylase". Biochemistry. 55 (14): 2163–2173. doi:10.1021/acs.biochem.6b00043. ISSN 0006-2960. PMC 4854488. PMID 27014926.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Joshi, Vijay; Penalosa, Arianne; Joshi, Madhumita; Rodriguez, Sierra (2021-05-18). "Regulation of Oxalate Metabolism in Spinach Revealed by RNA-Seq-Based Transcriptomic Analysis". International Journal of Molecular Sciences. 22 (10): 5294. doi:10.3390/ijms22105294. ISSN 1422-0067. PMC 8157348. PMID 34069886.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b Duncan, Sylvia H.; Richardson, Anthony J.; Kaul, Poonam; Holmes, Ross P.; Allison, Milton J.; Stewart, Colin S. (2002-8). "Oxalobacter formigenes and Its Potential Role in Human Health". Applied and Environmental Microbiology. 68 (8): 3841–3847. doi:10.1128/AEM.68.8.3841-3847.2002. ISSN 0099-2240. PMID 12147479.
{{cite journal}}: Check date values in:|date=(help) - ^ Duncan, Sylvia H.; Richardson, Anthony J.; Kaul, Poonam; Holmes, Ross P.; Allison, Milton J.; Stewart, Colin S. (2002-8). "Oxalobacter formigenes and Its Potential Role in Human Health". Applied and Environmental Microbiology. 68 (8): 3841–3847. doi:10.1128/AEM.68.8.3841-3847.2002. ISSN 0099-2240. PMID 12147479.
{{cite journal}}: Check date values in:|date=(help) - ^ Tanner, Adam; Bowater, Laura; Fairhurst, Shirley A.; Bornemann, Stephen (2001-11). "Oxalate Decarboxylase Requires Manganese and Dioxygen for Activity". Journal of Biological Chemistry. 276 (47): 43627–43634. doi:10.1074/jbc.m107202200. ISSN 0021-9258.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: unflagged free DOI (link) - ^ a b Pietzke, Matthias; Meiser, Johannes; Vazquez, Alexei (2020-03). "Formate metabolism in health and disease". Molecular Metabolism. 33: 23–37. doi:10.1016/j.molmet.2019.05.012. PMC 7056922. PMID 31402327.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Brosnan, Margaret E.; Brosnan, John T. (2016-07-17). "Formate: The Neglected Member of One-Carbon Metabolism". Annual Review of Nutrition. 36 (1): 369–388. doi:10.1146/annurev-nutr-071715-050738. ISSN 0199-9885.
- ^ Bank, RCSB Protein Data. "RCSB PDB - 1UW8: CRYSTAL STRUCTURE OF OXALATE DECARBOXYLASE". www.rcsb.org. Retrieved 2023-10-18.
- ^ Just, Victoria J.; Stevenson, Clare E.M.; Bowater, Laura; Tanner, Adam; Lawson, David M.; Bornemann, Stephen (2004-05). "A Closed Conformation of Bacillus subtilis Oxalate Decarboxylase OxdC Provides Evidence for the True Identity of the Active Site". Journal of Biological Chemistry. 279 (19): 19867–19874. doi:10.1074/jbc.m313820200. ISSN 0021-9258.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: unflagged free DOI (link) - ^ a b c Chakraborty, Subhra; Chakraborty, Niranjan; Jain, Deepti; Salunke, Dinakar M.; Datta, Asis (2002-9). "Active site geometry of oxalate decarboxylase from Flammulina velutipes: Role of histidine-coordinated manganese in substrate recognition". Protein Science : A Publication of the Protein Society. 11 (9): 2138–2147. ISSN 0961-8368. PMC 2373591. PMID 12192069.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Anand, Ruchi; Dorrestein, Pieter C.; Kinsland, Cynthia; Begley, Tadhg P.; Ealick, Steven E. (2002-06-01). "Structure of Oxalate Decarboxylase from Bacillus subtilis at 1.75 Å Resolution ,". Biochemistry. 41 (24): 7659–7669. doi:10.1021/bi0200965. ISSN 0006-2960.