004:211 Fall 2002

Chemical Catalysis in Biology

Course outline and Syllabus

Enzymes are the biological catalysts that direct, control and enhance the chemistry in biological systems. Those catalysts are mostly stereo- and regio-selective and specific. Their catalytic power is typically many orders of magnitude at ambient temperature and pressure. The structure and properties of protein and RNA enzymes will be studied. We will deliberate examples of enzymatic mechanisms and compare them to organic and inorganic catalytic processes. We will discuss the chemical and physical basis of their action, and how this understanding is used in the medical and chemical industries. For each topic, a variety of experimental methods and theoretical approaches will be presented. Practical and critical reading of recent literature will be exercised. Several investigators from the University’s staff will present advances in their current research.

The course material will be developed from text books and from recent journal articles. A list of topics is enclosed. There will be one midterm examination and a term paper in the form of an independent research proposal (in place of a final exam). The proposal will be presented orally to the class.

Principal Text:

"Structure and mechanism in protein science" Fersht A.

(W.H. Freeman and Company. 1998.) ISBN 0-7167-3268-8

Recommended Text:

"Mechanism in protein chemistry" Kyte, J.

(Garland Publishing, Inc. 1995) ISBN 0-8153-1700-X

"Biochemistry" 4th ed, Stryer, L.

(New York : W.H. Freeman, c1995) ISBN 0-7167-2009-4

"Catalysis in Chemistry and Enzymology" Jencks W.P.

(Dover, 1987)

Course Requirements:

Homework assignments will be given occasionally for topics where exercise is helpful. Grading will be divided as follows:

Homework: 10%

Midterm examination: 35%

Final proposal: 40%

Class presentation: 15%

Course Policies: It’s a graduate level course, meaning you are here because you are interested. The more you participate, the more you get out of it. Asking questions and reading the referred literature is highly encouraged.

Topics

* Chemical and biological catalysis.

The absolute rate theory

Principles of catalysis in chemistry and biology

Catalytic strategies

* Protein folding, structure and dynamics

From amino acids to three dimensional structure of proteins

Methods for determination

Concise review of protein folding

Protein dynamics-activity relationship

* Enzyme kinetics.

Introduction to kinetics (Steady state kinetics and pre-steady state kinetics)

Inhibition patterns as a mechanistic tool

Isotope effects

* Enzyme - ligand interactions.

Thermodynamics and kinetics

* Cofactors.

Chemical function of various coenzymes

* Posttranslational and chemical modifications.

Biogenesis and function of posttranslational aa derivatizations

Chemical modifications

* Metals and electron transfer.

Introduction to bio-inorganic chemistry of enzymes

* RNA catalysis.

Structure, function and applications

Implication to evolution (RNA world)

* Catalytic antibodies.

Introduction, principles and initial results

Recent findings and their applications to bio-catgalysis in general

* Extremophiles.

Stability and function of enzymes evolved under extreme conditions

Comparison to their mesophilic ("normal") analogues.

Implication to evolution (primitive enzymes?)

* Mechanistic examples.

Recent examples - the evolution of understanding mechanisms

Guests research talks

* Low - barrier hydrogen bond

* Concepts outside the main stream of enzymology

* Synthetic and industrial uses

Enzymes in organic solvents

Immobilized enzymes

* Approaches in drug development

Enzyme engineering

Biomimetic catalysts.