Aspartate Transcarbamoylase (ATCase): Difference between revisions
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== Structure == | == Structure == | ||
ATCase consists of two <scene name='58/581338/Catalytic_subunits/1'>catalytic</scene> trimers and three <scene name='58/581338/Regulatory_subunits/1'>regulatory</scene> dimers that are completely separable units. It has been documented that the subunits can even combine when mixed together, reconstituting the enzyme. The two catalytic trimers are arranged on top of each other, with three dimers of the regulatory chains combining them. Significant interactions between the regulatory dimers and catalytic trimers occur; such as catalytic trimer chains contacting structural domains in the regulatory unit that are stabilized by a <scene name='58/581338/Zn_domain/ | ATCase consists of two <scene name='58/581338/Catalytic_subunits/1'>catalytic</scene> trimers and three <scene name='58/581338/Regulatory_subunits/1'>regulatory</scene> dimers that are completely separable units. It has been documented that the subunits can even combine when mixed together, reconstituting the enzyme. The two catalytic trimers are arranged on top of each other, with three dimers of the regulatory chains combining them. Significant interactions between the regulatory dimers and catalytic trimers occur; such as catalytic trimer chains contacting structural domains in the regulatory unit that are stabilized by a <scene name='58/581338/Zn_domain/3'>zinc</scene> atom bound to four cysteine residues. ATCase is largely alpha helical with large changes in quaternary structure occurring (trimers move 12 Angstroms apart and rotate approximately 10 degrees) upon <scene name='58/581338/Pala/1'>PALA</scene> binding (a bisubstrate analog that resembles an intermediate). The <scene name='58/581338/Pala_interactions/1'>PALA interactions</scene> are as shown. | ||
== Function == | == Function == | ||
Aspartate Transcarbamoylase catalyzes the first step in the biosynthesis of pyrimidines ( specifically called N-carbamoyl-aspartate) which ultimately yield pyrimidine nucleotides such as CTP. The cell must precisely regulate the amount of CTP in the cell because making it can be energetically expensive. Therefore, the rate of reaction catalyzed by ATCase is fast at low [CTP] but slows as [CTP] increases. However, CTP is quite different than the active site of ATCase, so at high levels it effectively inhibits the enzyme by binding to an allosteric/regulatory site rather than the active site. ATCase is a textbook example of a molecule under allosteric regulation in which the binding of substrate to one active site in a molecule increases the likelihood that the enzyme will bind more substrate, a phenomena called cooperativity. | Aspartate Transcarbamoylase catalyzes the first step in the biosynthesis of pyrimidines ( specifically called N-carbamoyl-aspartate) which ultimately yield pyrimidine nucleotides such as CTP. The cell must precisely regulate the amount of CTP in the cell because making it can be energetically expensive. Therefore, the rate of reaction catalyzed by ATCase is fast at low [CTP] but slows as [CTP] increases. However, CTP is quite different than the active site of ATCase, so at high levels it effectively inhibits the enzyme by binding to an allosteric/regulatory site rather than the active site. ATCase is a textbook example of a molecule under allosteric regulation in which the binding of substrate to one active site in a molecule increases the likelihood that the enzyme will bind more substrate, a phenomena called cooperativity. | ||
Revision as of 20:15, 22 April 2014
StructureStructure
This is the beginning of a page about Aspartate Transcarbamoylase (ATCase). You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue. StructureATCase consists of two trimers and three dimers that are completely separable units. It has been documented that the subunits can even combine when mixed together, reconstituting the enzyme. The two catalytic trimers are arranged on top of each other, with three dimers of the regulatory chains combining them. Significant interactions between the regulatory dimers and catalytic trimers occur; such as catalytic trimer chains contacting structural domains in the regulatory unit that are stabilized by a atom bound to four cysteine residues. ATCase is largely alpha helical with large changes in quaternary structure occurring (trimers move 12 Angstroms apart and rotate approximately 10 degrees) upon binding (a bisubstrate analog that resembles an intermediate). The are as shown. FunctionAspartate Transcarbamoylase catalyzes the first step in the biosynthesis of pyrimidines ( specifically called N-carbamoyl-aspartate) which ultimately yield pyrimidine nucleotides such as CTP. The cell must precisely regulate the amount of CTP in the cell because making it can be energetically expensive. Therefore, the rate of reaction catalyzed by ATCase is fast at low [CTP] but slows as [CTP] increases. However, CTP is quite different than the active site of ATCase, so at high levels it effectively inhibits the enzyme by binding to an allosteric/regulatory site rather than the active site. ATCase is a textbook example of a molecule under allosteric regulation in which the binding of substrate to one active site in a molecule increases the likelihood that the enzyme will bind more substrate, a phenomena called cooperativity. MechanismATCase displays features of a concerted mechanism due to the fact that changes in the enzyme are "all or none". In Michaelis-Menten kinetics, ATCase's curve is sigmoidal exemplifying a union of the R (active) and T (tense) states. High concentrations of CTP shift the curve right towards the T state, whereas high concentrations of ATP shift the curve left towards the R state.
Structural highlightsThis 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.
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ReferencesReferences
Berg, Jeremy M., John L. Tymoczko, and Lubert Stryer. Biochemistry. Intl Seventh ed. New York: W.H. Freeman and Company, 2012. Print. p 300-306
- ↑ 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