Chapter 2: Protein Interactions pp. 38-44

Let’s look at how proteins interact

Proteins as: Proteins as: Enzymes Transporters Signals Receptors Binding proteins Regulatory proteins Immunoglobulins

An enzyme at work CARBONIC ANYDRASE CO2 + H20 H2CO3

Protein transporter (one example there are many more!) http://www.stolaf.edu/people/giannini/biological%20anamations.html

Cell Signaling through various processes will be discussed in detail in chapter 5) Ligand and receptors Why do we care?? Normal Cells respond to cell signals! And Abnormal cells respond to cell signals!!

Equilbrium Constant Keq Keq=[P][L]\[PL] Refers to the ratio of bound ligand verus unbound ligand Quantitative expression Keq is called dissociation constant or Kd. What would a “large Kd value” tell you about a drug versus a “drug with a smll Kd value”?

Chapter 2: Protein Interactions pp. 38-44

Isoforms of hemoglobin Fetal hemoglobin has lower Kd for O2 than adult hemoglobin. What does this mean physiologically?

Ligands can sometimes mimic another ligand for a protein. Nicotine Acetylcholine

Proteins as Immunoglobulins

Protein Binding to a substrate (ligand) Can be affected by: Cofactors interacting with the protein Proteolytic activation of the protein Modulators (there are different modulators) Protein: for example an enzyme Substrate/ligand

Cofactors: enzymes may have requirements in order to work…

Cofactors: non-organic For example: Mg++, Ca++, Cl- May be required for enzyme activity! and Co-Enzymes!

Proteolytic activity of a digestive enzyme

Competitive inhibitor is an example of a “reversible modulator”

Example of Reversible antagonist Ritonavir: protease inhibitor http://pharmacologycorner.com/hiv-protease-inhibitors-animation-showing-their-mechanism-of-action/

However some Modulators ar irreversible inhibitors Tamoxifen and breast cancer treatment For example: penicillin

Most enzymes have modulators to be optimally active… Modulators assist in providing ideal conformation for reactions

Figure 2-20 - Overview

Covalent Modulation Kinase activity (exchange reaction) Phosphatase activity (remove group reaction)

pH and temperature

We regulate the amount of protein made:

The body regulates the… Amount of proteins we make (example) Glucagon increases blood glucose Insulin decreases blood glucose Up regulation GLUCAGON Down regulation INSULIN HOMEOSTASIS 

FOR EXAMPLE GLLUCOSE Figure 2-23