Covalent Modulation

The second way to alter the shape and therefore the activity of a protein is by the covalent bonding of charged chemical groups to some of the protein's side chains. This is known as covalent modulation. In most cases, a phosphate group, which has a net negative charge, is covalently attached by a chemical reaction called phosphorylation, in which a phosphate group is transferred from one molecule to another. Phosphor-ylation of one of the side chains of certain amino acids in a protein introduces a negative charge into that region of the protein. This charge alters the distribution of electric forces in the protein and produces a change in protein conformation (Figure 4-7b). If the confor-mational change affects a binding site, it changes the binding site's properties. Although the mechanism is completely different, the effects produced by covalent modulation are the same as those of allosteric modu-lation—that is, a functional binding site may be turned on or off or the affinity of the site for its ligand may be altered. To reiterate, unlike allosteric modulation, which involves noncovalent binding of modulator molecules, covalent modulation requires chemical reactions in which covalent bonds are formed.

Most chemical reactions in the body are mediated by a special class of proteins known as enzymes, whose properties will be discussed in Section B of this chapter. For now, suffice it to say that enzymes accelerate the rate at which reactant molecules (called substrates) are converted to different molecules called products. Two enzymes control a protein's activity by covalent modulation: One adds phosphate, and one removes it. Any enzyme that mediates protein phosphorylation is called a protein kinase. These enzymes catalyze the transfer of phosphate from a molecule of adenosine triphosphate (ATP) (discussed in Section B of this chapter) to a hydroxyl group present on the side chain of certain amino acids:

Protein + ATP

protein kinase

The protein and ATP are the substrates for protein ki-nase, and the phosphorylated protein and adenosine diphosphate (ADP) are the products of the reaction.

There is also a mechanism for removing the phosphate group and returning the protein to its original shape. This dephosphorylation is accomplished by a second enzyme known as phosphoprotein phos-phatase.

phosphoprotein phosphatase

Protein + HPO42~

The activity of the protein will depend on the relative activity of the kinase and phosphatase that con-

TABLE 4-1 Factors that Influence Protein Function

Changing protein shape a. Allosteric modulation b. Covalent modulation ^■i. Protein kinase activity ii. Phosphoprotein phosphatase activity

Changing protein shape a. Allosteric modulation b. Covalent modulation ^■i. Protein kinase activity ii. Phosphoprotein phosphatase activity trol the extent of the protein's phosphorylation. There are many protein kinases, each with specificities for different proteins, and several kinases may be present in the same cell. The chemical specificities of the phos-phoprotein phosphatases are broader, and a single enzyme can dephosphorylate many different phosphor-ylated proteins.

An important interaction between allosteric and covalent modulation results from the fact that protein kinases are themselves allosteric proteins whose activity can be controlled by modulator molecules. Thus, the process of covalent modulation is itself indirectly regulated by allosteric mechanisms. In addition, some allosteric proteins can also be modified by covalent modulation.

In Chapter 7 we will describe how cell activities can be regulated in response to signals that alter the concentrations of various modulator molecules that in turn alter specific protein activities via allosteric and covalent modulations. Table 4-1 summarizes the factors influencing protein function.

SECTION A SUMMARY

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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Responses

  • Alvisa
    What enzyme removes the phosphate group from a covalently modulated protein?
    6 years ago
  • Miley Dickson
    What is the difference between allosteric and covalent modulation?
    6 years ago
  • Juan
    What are covalently modulation enzyme?
    6 years ago
  • semira mewael
    What enzymes directly covalently modulates a protein?
    6 years ago
  • Regolo
    How is the activity of an allosteric protein modulated?
    6 years ago
  • BANAZIR BUTTON
    How is enzyme activity regulated by covalent modulation?
    6 years ago
  • gundobad
    Which factors can be changed to influence an allosteric protein's activity?
    6 years ago
  • KATIE
    Which enzyme is in covalent modulation to remove electric charged group?
    6 years ago
  • Mary Price
    What type of enzyme removes the phosphate group from a covalently modulated protein?
    3 years ago
  • SHAWN MERCADO
    Which are the types of modulator enzymes?
    9 months ago

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