Chapter 14

Chapter 14 - Chapter 14 Role of Transition-State...

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Unformatted text preview: Chapter 14 Role of Transition-State Stabilization in Enzyme Catalysis o enzyme role: to reduce energy barrier btwn substrate and transition state via ES complex o enzyme must stabilize the transition structure more tightly than the substrate. Magnitudes of Enzyme-Induced Rate Accelerations o enzyme catalyzed rxns usually are 10 7 10 14 times faster than uncatalyzed counterparts o catalytic mechanisms (aka factors) that contribute to enzyme performance entropy loss in ES formation ES more organized than E+S in soln. both E and S loose translational and rotational entropies when E and S interact to form one molecule thus T S is + compensates for some G b (see below) destabilization of ES due to strain/desolvation/electrostatic effects keeps G b from getting too big enzyme designed to bind to transition state more strongly than the substrate imperfect fit when S binds to E results in strain/distorntion charged groups in S are desolvated when moving into E active site results in less stability/more reactivity substrate w/ unfavorable charges/sign electrostatic effects covalent catalysis some rxns get much of rate accelerat ion from format ion of covalent bonds btwn E and S given BX + Y BY + X and BX + Enz E:B + X + Y BY + Enz o acceptor on E must be better attacking group than Y and better leaving group than X side chains (am ines/carboxylates/aryl and alkyl hydroxyls/im idazoles/thiol groups) have variety of nucleophilic centers for catalysis o these attack elect rophilic centers (phosphoryl/acyl/glycosyl groups) of substrates E- S intermediate attacked by water/next substrate to give product covalent elect rophilic catalysis observed also, but involves coenzyme adducts that generate electrophilic centers general acid/base catalysis (2 types: specific and general) specific: involves H + or OH- o rate depends on pH, but buffer has no effect o graph is consecutive flat lines (for constant pH) general: involves acids and bases other than H + and OH- (facilitate transfer of H + in the transition state) o buffer may donate/accept H + in transition state o rate depends on buffer concentration o graph is increasing slope of flat lines (for constant pH) low barrier H-bonds: when barrier to H exchange dropped to the point that it is at/below -=pt energy level o H H free to move anywhere btwn 2 O (or any 2 heteroatoms) as distance between heteroatoms becomes smaller, H bonds become st ronger, H becomes centered, bond order approaches 0.5 for both O-H interactions (nearly covalent) o stabilizat ion energies can approach 60 k J/mol in solut ion (much higher than normal H-bond) o pK a values of the two electronegative atoms must be similar energy relased in forming the LBHB is used to help rxn which forms it, lowering the activation barrier fro the rxn o or LBHB redistributes e- density in reactive intermediate (rate acceleration achieved by...
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Chapter 14 - Chapter 14 Role of Transition-State...

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