Chapter 2:Protein Interactions

pp. 38-44

Let’s look at how proteins interact

Proteins as:

• Enzymes• Transporters• Signals• Receptors• Binding proteins• Regulatory proteins• Immunoglobulins

Proteins as:

An enzyme at work

CO2 + H20 H2CO3

CARBONIC ANYDRASE

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)

Why do we care??

Normal Cells respond to cell signals!

And Abnormal cells respond to cell signals!!

Ligand and receptors

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)

Substrate/ligand

Protein: for example an enzyme

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

For example: penicillin

Tamoxifen and breast cancer treatment

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

Figure 2-23

FOR EXAMPLEGLLUCOSE