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/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. | 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 should be noted that this scene is only looking at one set of regulatory and catalytic subunits not all of them for the sake of visualization. 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. | ||