Substrate regulation site

The polypeptide chain of PDC is organized in three domains. The amino-terminal domain (a) binds the pyrimidine ring, whereas the carboxy-terminal domain (y) forms the diphosphate binding site, while the middle domain ((1) performs the intermolecular contact between the two dimeric halves in the tetramer and contains the substrate regulation site in PDCS.c. (details about the substrate regulation behaviour in PDCS.c. are discussed in Sects. 4 and 6.1). 

We consider here the case where the absorbent molecule (the enzyme) has one active site A for binding the substrate A, and one regulator site R for the effector R (Figure 8.7). We assmne that the two sites A and R are far apart, so that direct... 

FIGURE 12-44 Regulation of CDK by phosphorylation and proteolysis. (a) The cyclin-dependent protein kinase activated at the time of mitosis (the M phase CDK) has a "T loop" that can fold into the substrate-binding site. When Thr150 in the T loop is phosphorylated, the loop moves out of the substrate-binding site, activating the CDK... 

Regulation at primary regulatory sites " St ATP Q 0 0 Regulation at substrate-specificity sites " Q (d)ATP ... 

Substrate specificity site The binding of nucleoside triphosphates to an additional allosteric site (known as the substrate specificity site) on the enzyme regulates substrate specificity, causing an increase in the conversion of different species of ribonucleotides to deoxyribonucleotides as they are required for DNA synthesis. 

Briand, L., Chobert, J.-M., Tauzin, J., Declerck, N., Leonil, J., Molle, D., Tran, V., and Haertle, T. 1997. Regulation of trypsin activity by Cu2+ chelation of the substrate binding site. Protein Engng 10, 551—560. 

Some positive regulators act by raising the affinity of all substrate binding sites (catalytic sites) to the maximum, independent of [S], thus destroying the cooperativity and raising the reaction rate at low [S], An example of this behavior is the regulation of phosphofructokinase by AMP (adenosine 5 -phosphate). 

While competitive inhibition depends on a close structural relationship between the inhibitor and the normal substrate, certain enzymes may have their activity modified by metabolites which bear no structural relationship to the substrate and which bind reversibly to a site on the enzyme surface which is quite distinct from the substrate-binding site. This is known as the allosteric site. It is believed that allosteric regulators act by modifying the conformation of the active site so that it binds the substrate either more positive effectors or activators) or less negative effectors or inhibitors) strongly. The allosteric site is not necessarily close to the active site and may even be situated on a different type of subunit from the active site. 

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