5-Enzyme mechamism handout3

4 nucleophilic acyl substitution nas base catalysis

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: bilization Acid/base catalysis Specificity 3. Chymotrypsin: (Example 2) Reaction cycle Covalent catalysis Acid/base catalysis Transition state stabilization Chymotrypsin: Covalent catalysis (E-S bond) sitsonserine ES complex onenzyme,O- isnucleophile,attackscarbonyl, 2 formsbond O-Cbond,betweencovalentbondform 3 enzymeholdssubstrate,stabilizes anythinginbetween,making Product covalentbonds*** #1 tetrahedralintermediate 4 1 7 EP complex acylintermediate tetrahedralintermediate 5 6 Nucleophilic acyl substitution (NAS): Tetrahedral intermediate (from Chem 233) Overview 1. Introduction: Thermodynamics vs. kinetics Catalysis Enzyme catalysis 2. RNase: (Example 1) Function, structure, reaction Mechanism without catalysis Transition state stabilization Acid/base catalysis Specificity 3. Chymotrypsin: (Example 2) Reaction cycle Covalent catalysis Acid/base catalysis Transition state stabilization Chymotrypsin: Acid/base catalysis 2 -> 3: His-57 first acts as a base to abstract the proton from Ser-195, thus generating a stronger nucleophile. 2 ES complex OHcomingfromtheenzyme, notfromthesubstrateasinRNAse Tetrahedral intermediate acidcomesin,betterleavinggroup 3 byprotonating.acidisthe conjugateacidofthebaseofsame Product histidine. #1 Sameprinciplethough basemakesstrongernuclephile 3 -> 4: Protonated His-57 then acts as an acid to donate a proton to the amide N, thus generating a good leaving group. 4 Nucleophilic acyl substitution (NAS): Base c...
View Full Document

This note was uploaded on 04/01/2014 for the course BIOL 201 taught by Professor Chowrira during the Winter '13 term at UBC.

Ask a homework question - tutors are online