Lecture 4 Web: pollev.com/ucibio Text: To: Type in:

Enzymes and reactions Spontaneity = ___ Enzyme = Decrease G# = _________________ Mechanism = “Induced fit” Rate = ___ “Active site” ________________ stabilize TS

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

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

Glc  Glc-6-P: Enzyme = Hexokinase

Specificity of enzymes - Isomers

Specificity of enzymes - Stereoisomers

Effects of specificity – Tastes!

Effects of specificity – Calories!

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 _____ group and ___________ group Each amino acid has a different “R” group There are _____ different amino acids H2NH2NCOOHC R H

Amino acids, pH and charge

Amino acid titration curve

Asp titration curve

Amino acids in cells… H2NH2NCOOHC R H

The Peptide bond: Joining amino acids

Nomenclature: N t -> C t

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?