08-Enzyme Regulation

08-Enzyme Regulation - Protein Activity Regulation...

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Protein Activity Regulation Allosteric Control Allosteric proteins contain distinct regulatory (allosteric) and functional sites. Binding of regulatory molecules (usually small) at the allosteric sites trigger conformational changes that are transmitted to the active site(s). Many allosteric proteins show cooperativity: activity at one functional site affects the activity at others. Changes in substrate concentration can affect activity significantly. Multiple Forms Isozymes: homologous enzymes within an organism that catalyze the same reaction, differing in structure, K M , V max , and regulatory properties. Certain isozymes may be expressed in distinct tissue, organelle or stage of development. Reversible Covalent Modification Catalytic properties of enzymes can be altered significantly upon covalent attachment of a modifying group such as phorphoryl group. Protein kinases attach phosphoryl groups onto proteins. Protein phosphatases remove phosphoryl group from proteins. Proteolytic Activation Many enzymes are synthesized as inactive precursors called zymogens or proenzymes. The zymogen is then converted irreversibly into the active enzyme by hydrolysis. Expression Natural Inhibitors
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Aspartate Transcarbamoylase (ATCase) Aspartate transcarbamoylase (ATCase) Catalyzes the condensation of aspartate and carbamoylphosphate to form N- carbamoylaspartate, The first step in pyrimidine biosynthesis; pyrimidines are components of nucleic acids (DNA, RNA). ATCase is inhibited by cytidine triphosphate (CTP), the final product of the ACTase-controlled pathway. Feedback, or end product inhibition. CTP does not resemble any of the substrates. CTP binds a site distinct from the active site, called allosteric (Greek allos, ‘other’, and stereos, ‘structure’), or regulatory sites. CTP is an allosteric inhibitor.
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ATCase: Catalytic and Regulatory Subunits ATCase can be separated into two kinds of subunits by treatment with p -hydroxymercuribenzoate. p -Hydroxymercuribenzoate reacts with sulfhydryl groups. The sedimentation coefficient of relevant molecules: native enzyme 11.6S, dissociated subunits 2.8S and 5.8S. The two subunits can be separated by ion exchange or centrifugation. The larger subunit is the catalytic subunit (c). Activity independent of CTP. 3 chains, 34 kd each, c 3 . The smaller subunit is the regulatory subunit (r). No activity, but binds CTP. 2 chains, 17 kd each, r 2 . Reconstituted enzyme consists of 6 catalytic and 6 regulatory subunits to give c 6 r 6 , showing same allosteric behavior as native enzyme.
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3D Structure of ATCase The structure of ATCase have been solved by crystallography (Lipscomb) Two catalytic trimers are stacked one on top of the other, linked by three dimers of the regulatory chains. Each r chain within a regulatory dimer interacts with a c chain
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This note was uploaded on 11/10/2010 for the course CHE Biochem taught by Professor Disney during the Spring '10 term at SUNY Buffalo.

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08-Enzyme Regulation - Protein Activity Regulation...

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