Lecture 4 Web: pollev.com/ucibio Text: To: 37607 Type in: 169964 <your question>

Lecture 4 objectives Understand how active sites increase reaction rates Understand the specificity of enyzmes Know the structure and properties of amino acids Know the functional groups and characteristics of amino acids

Enzymes and reactions Spontaneity = DG Rate = DG# Enzyme = Decrease DG# = Increase rate Mechanism = “Induced fit” “Active site” weak interactions stabilize TS

Decreasing DG‡: Proximity + Orientation Active site: Bring products together In precise orientation

Not just binding! Forces change in substrate conformation as well! Keep molecules under “strain” to facilitate reaction Active site interactions can stabilize the TS Active site residues can initiate reactions Different enzymes = Different mechanisms

Glc  Glc-6-P: Enzyme = Hexokinase http://web.chem.ucsb.edu/~molvisual/ABLE/induced_fit/index.html

Specificity of enzymes - Isomers

Specificity of enzymes - Stereoisomers

Effects of specificity – Tastes!

Effects of specificity – Calories! http://commons.wikimedia.org/wiki/File:D_et_l_glucose.png

Effects of specificity – Treatment!

3D shape is important! OK. Fine. So the shape of the active site is important How is the shape formed?

Formation of active sites

Active site review Small part of total enzyme 3D architecture is important Specific residues important Not necessarily contiguous residues

How does an active site form? Protein must “fold”into structure How does protein “fold?” First, understand protein composition Proteins made up of _____________

What is an amino acid? Molecule with amino group and carboxylic acid group H2N COOH C R H Each amino acid has a different “R” group There are _____ different amino acids

Amino acids, pH and charge

Amino acid titration curve

Asp titration curve

Amino acids in cells… H2N COOH C R H

The Peptide bond: Joining amino acids

Nomenclature: Nt -> Ct

Charge on peptides is cumulative

OK. What does this all have to do with enzymes? What is needed for proteins to fold correctly? Can we design experiment to test?