Subunit allosterism role

We have found that the communication between Ca2+ sparks and BK channels can be tuned by membrane potential (this study, Herrera et al 2001) and by the accessory / subunit (Brenner et al 2000, Petkov et al 2001). This effect can be accounted for based on the allosteric relationship between the BK channel voltage and Ca2+ sensors, whereby membrane potential depolarization favours a channel conformation that has a higher Ca2+ sensitivity. The /b subunit has a similar role to increase the apparent Ca2+ sensitivity of the a subunit. 

The topologically defined region(s) on an enzyme responsible for the binding of substrate(s), coenzymes, metal ions, and protons that directly participate in the chemical transformation catalyzed by an enzyme, ribo-zyme, or catalytic antibody. Active sites need not be part of the same protein subunit, and covalently bound intermediates may interact with several regions on different subunits of a multisubunit enzyme complex. See Lambda (A) Isomers of Metal Ion-Nucleotide Complexes Lock and Key Model of Enzyme Action Low-Barrier Hydrogen Bonds Role in Catalysis Yaga-Ozav /a Plot Yonetani-Theorell Plot Induced-Fit Model Allosteric Interaction... 

Phosphorylation of glycogen phosphorylase is the initiator for the coupled conformational changes, which are coimmmicated over a large distance to the active site. Similar to the allosteric mechanism of phophofructokinase, the inter-subunit contact sinfaces play a decisive role for the communication between the phosphorylation site... 

A relative of the kinases is adenylate cyclase, whose role in forming the allosteric effector 3, 5 -cyclic AMP (cAMP) was considered in Chapter 11. This enzyme catalyzes a displacement on Pa of ATP by the 3 -hydroxyl group of its ribose ring (see Eq. 11-8, step a). The structure of the active site is known.905 Studies with ATPaS suggest an in-line mechanism resembling that of ribonuclease (step a, Eq. 12-25). However, it is Mg2+ dependent, does not utilize the two-histidine mechanism of ribonuclease A, and involves an aspartate carboxylate as catalytic base.906 All isoforms of adenylate cyclase are activated by the a subunits of some G proteins (Chapter 11). The structures907 of Gsa and of its complex with adenylate kinase905 have been determined. The Gsa activator appears to serve as an allosteric effector. 

Effector binding, per se, is the most direct output of Ga activation, and this event may be sufficient to account for the mechanism of PDE activation, in which Gat binds and sequesters the inhibitory subunit of the enzyme complex. Thus, the C-terminal residues of PDEy responsible for inhibition of the catalytic PDE a/) heterodimer are sequestered in the interaction with Gat (Brown, 1992 Lipkin et al., 1988). In other systems, Ga are allosteric activators or inhibitors, or act in more subtle and less well-understood roles as organizing centers of G protein-signaling complexes. 

The answer is c. (Murray, pp 375-401. Scriver, pp 2513-2570. Sack, pp 121-138. Wilson, pp 287-320.) The steps of pyrimicfine nucleotide biosynthesis are summarized in the figure below. The first step in pyrimidine synthesis is the formation of carbamoyl phosphate. The enzyme catalyzing this step, carbamoyl phosphate synthetase (1), is feedback-inhibited by UMP through allosteric effects on enzyme structure (not by competitive inhibition with its substrates). The enzyme of the second step, aspartate transcarbamoylase, is composed of catalytic and regulatory subunits. The regulatory subunit binds CTP or ATP TTP has no role in the feedback inhibition of pyrimidine synthesis. Decreased rather than increased activity of enzymes 1 and 2 would be produced by allosteric feedback inhibition. 

The interface between the subunits often plays a central role in allosteric regulation by allowing the coupling of conformational changes within one subunit to the other. 

This approach has been used to study the role of a-subunit structural elements in catalysis and allosteric interactions. One example is the replacement of Arg by Leu at position 17 9 (aRl 9 7 L) of the a-subunit. This residue resides within... 

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