生物化学原理教学（杨荣武）Chapter10 Mechanisms of enzyme catalysis.pptVIP

Chapter 10 Mechanisms of Enzyme Catalysis Outline Major methods for studying enzyme mechanisms “The transition-state stabilization” theory Mechanisms of transition state stabilization Proximity and Orientation General Acid-base catalysis Electrostatic catalysis Metal catalysis Covalent catalysis Substrate strain Structure and function of several common enzymes Proteases Lysozyme (self-study) Major methods for studying enzyme mechanisms Find out the conservative residues by aligning homologous enzymes Study the 3-D structure of enzymes Perform site-directed mutagenesis Carry out the kinetic analysis Make chemical modification Molecular Computer Mimics Evidences of stabilizing the transition state of the reaction Transition analogues are potent inhibitors Abzymes Enzymes have evolved to recognize the transition state of the reaction they catalyze To design an enzyme inhibitor, we should try to mimic the transition state of the reaction, not the substrates or products An example - tetrahydrouridine is a transition state analogue of cytidine deaminase Antibodies are immunoglobulins. Antibodies are elicited in an organizm in response to immunological challenge by a foreign molecule called antigens; Antibodies elicited in response to transition state analogs have the ability to stabilize the transition state and thus can catalyze a reaction by forcing the substrate into the transition state structure; Examples of abzymes: How do enzymes stabilize the transition state of a reaction Catalysis by proximity and orientation General Acid-base catalysis Electrostatic catalysis Metal catalysis Covalent catalysis Substrate strain Catalysis by proximity and orientation This increases the rate of the reaction as enzyme-substrate interactions align reactive chemical groups and hold them close together. This reduces the entropy of the reactants and thus makes reactions such as ligations or addition reactions more favorable, there is a reduction in the overall loss of ent