General Description: This course is designed to introduce graduate students with little or no background in biochemistry to the techniques and theories of modern bioorganic chemistry. Much of the course will focus on understanding the chemical strategies and mechanisms behind enzyme catalysis. Key concepts in the biosynthesis of natural products will also be presented. Students will also be exposed to topics that have appeared in the recent literature. Although not absolutely essential, it is strongly recommended that students have taken a 3rd year-level course in organic chemistry.
Recommended Text: No text is required for the course, but it is strongly recommended that students reference Introduction to Enzyme and Coenzyme Chemistry by T.D.H. Bugg (available for purchase as a Kindle, or available at Woodward library).
Evaluation:
- Problem sets (10% of mark, best 5/6 counted)
- Short presentation (10%)
- Short article (15%)
- Midterm (20%)
- Final (45%)
Instructor: Prof. Katherine Ryan, A249 Chem./Phys. Building, ksryan@chem.ubc.ca
Outline:
Intro: Introduction to enzymes as protein-based catalysts; biocatalysis; metabolism; antibiotic drug development; structure of enzymes; folding forces; active sites
Enzymatic catalysis: How enzymes catalyze reactions; transition-state stabilization; acid-base catalysis; comparing enzymes to traditional organic chemistry
Enzyme kinetics: Michaelis-Menten kinetics, inhibition kinetics, kinetic isotope effects; concept of the perfect enzyme
How enzymes work:
- Proteases
- Glycosidases
- Phosphatases
- ATP-dependent ligases
- Glycosyltransferases
- Dehydrogenases
- Transient oxidation
- Reactions with oxygen
- Aldolases
- CO2 fixation and carboxylation
- Thiamine diphosphate
- S-adenosylmethionine
- Pyridoxal phosphate
- Vitamin B12 and radical SAM enzymes
Biosynthesis: Polyketide synthases, non-ribosomal peptide synthetases, terpene cyclases, alkaloid biosynthesis
Additional topics: Computational protein design, directed evolution, ancestral protein reconstruction, structural biology, biocatalysis, antibiotic drug development and emergence of drug resistance