Proteins: Globular and Membrane

Proteins: Globular and Membrane

Globular Proteins:

>Soluble.

> Most enzymes are globular.

>The primary way globular proteins maintain their tertiary structure is called the Hydrophobic Effect.

Charged, polar hydrophilic residues on the surface.

Non-polar residues seclude themselves in a hydrophobic "core" area.

> Other ways of maintaining 3⁰ structure "Salt Bridges" and "Disulfide Bridges"

One feature that most globular proteins share is the ability to bind certain small molecules.

The site where binding occurs is the active site.

The small molecules that bind are called substrates.

The most common type of globular protein that is capable of binding a small molecule is an enzyme.

Enzymes:

Are Globular Proteins.

Are catalytically active proteins which convert substrate to product.

Are specific for their substrate and reaction.

Often require a supplementary chemical group or

CO-FACTORS-

Most enzymes require a supplementary chemical group, called a co-factor,to be fully active. There are organic and inorganic co-factors, many enzymes contain both.

Oraganic: there are two types, co-enzymes and prosthetic groups.

Co-enzyme	Prosthetic Group
Soluble, easily removed	Covalently Attached

Inorganic:

Fe, Cu, Mg

Glycoproteins:

>Globular proteins, especially those in circulation, are often modified to increase solubility and enhance biological activity.

>One method is by the covalent attachment of a sugar unit, glycosylation ------> glycoprotein
>The variety of sugars, sugar modifications and different linkages give glycoproteins a very high information content.

Enzymatic Glycosylation

>enzyme directed, specific

>generally involves "anhydride" formation

R₁-OH HO-R_{2 -------->
R1-O-O-R2}

Non-Enzymatic Glycosylation

>non-specific

> "Schiff" base formation

Membrane Proteins:

>often contain a globular domain

> are anchored to a membrane

>can be categorized as:

Receptors-extracellular globular domains can bind specific molecules such as, hormones.

Transporters-span the membrane, allow passage of molecules across the membrane.
Cell-Cell Recognition Proteins-usually glycoproteins, high information content allows very specific interactions between cells.

Fibrous (Structural) Proteins:

>insoluble

>have one repeating secondary structural pattern (motif)

>important "structural" components in the body

>framework of connective tissue, muscle etc.

>collagen

Clinical Correlate: Non-Enzymatic Glycosylation

>In diabetic patients, blood sugar can reach very high levels ------> the aldehyde groups on these glucose molecules can spontaneously react with free amines on circulating proteins.

>Since Hb is an abundant blood protein, it is frequently glycosylated in a "non-enzymatic" fashion.
>Short-term ("schiff" base formation) non-enzymatic glycosylation is reversible.
>If glucose levels remain uncontrolled for months (long-term), the attached glucose will form a non-reversible cross-link with a second amino group.
>These compounds are called Advanced Glycosylation Endproducts (AGE's).

>AGE's can be measured and are a good indicator of long term blood glucose control in the diabetic patient.