ch14partiii重点整理whatcanbelearnedfromtypicalenzyme.pptVIP

Typical enzymes Serine protease Aspartic protease Chorismate Mutase Zymogen/proenzyme (inactive enzyme precursor) Feed forward reaction (positive feedback) Catalytic triad (Ser His Asp) Substrate-binding pockets (selectivity) Ser (covalent bond) His (general acid/base) Asp (orient His) Mechanism Detail Transition-State Stabilization Two-lobed structure Mechanism (LBHB catalysis) Ex : HIV-1 protease Inhibitor drugs Intramolecular rearrangement Via chair Mechanism and Transition State Analog (TSA) Near-Attack complex (NAC) Ch14 Part III 重點整理What Can Be Learned From TypicalEnzyme Mechanisms? 例一: The serine protease: → covalent catalysis, general acid-base catalysis, substrate selectivity, LBHB Part III用三種酵素的例子來描述前面提過的mechanisms: 例二: The aspartic protease: →general acid-base catalysis, LBHB 例三: Chorismate mutase: → NAC The serine protease: (以Ser為活性中心的蛋白酶) Serine protease family 包含: -消化道酵素:typsin, chymotrypsin, elastase (分泌時以zymogens型態出現) - 凝血蛋白酶:Thrombin (詳見Ch15) Zymogen (酵素前驅物) 經水解反應 (hydrolysis) 或構形改變 (configuration change) 使active site 暴露 Active enzyme *Positive feedback 可自身活化 Catalytic Triad (三個主要的活性中心) His57, Asp102, Ser195 Covalent catalysis general acid-base catalysis 詳見: “The Serine Protease Mechanism in Detail” (p.62~p.65) Substrate selectivity →利用酵素的立體構造 去適應基質 Trypsin: 切帶正電、長側鏈的基質 Elastase: 切立體阻礙小的基質 Chymotrypsin: 切疏水性的芳香族 呈現黃色! 故可藉顏色變化來評估酵素的活性! p -Nitrophenylacetate Transition-State Stabilization in the Serine Proteases ? The chymotrypsin mechanism involves two tetrahedral oxyanion intermediates ? These intermediates are stabilized by a pair of amide groups that is termed the “oxyanion hole” 例二: The aspartic protease: →general acid-base catalysis, LBHB ? All involve two Asp residues at the active site ? These two Asp residues work together as general acid-base catalysts ? Most aspartic proteases have a tertiary structure consisting of two lobes (N-terminal and C-termin