BCHE 395-14 2013 Chymotrypsin Mechanism

What if the muta6on was a conserved change 22

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Unformatted text preview: rogen Bond (LBHB) •  Special type of H- bond because of its strength (pg. 218) –  Strong because the distance between acceptor and donor is especially short •  Chymotrypsin à༎ Substrate binding causes subtle change in conforma6on •  Compresses H- bond between His57 and Asp102 •  Causes the increase of pKa of His57 from ~7 to >12 •  So His57 wants to be protonated! Takes H+ from Ser195 hydroxyl group pK ~7 à༎ pK >12 Resonance structure 19 Ac6ve Site of Chymotrypsin with Substrate •  Other Amino acids Oxyanion Hole •  (1) Gly193/Ser195: oxyanion hole Gly193 •  Enzyme pocket which stabilizes a deprotonated oxygen or alkoxide (O- ) •  In this case, O- H- bonds to Gly193 and Ser195 (amide N- H) •  (2) Ile 16: cri6cal ionic interac6on with Asp194 Ser195 hlp://upload.wikimedia.org/wikibooks/en/thumb/e/ef/ Oxyanion_hole.png/220px- Oxyanion_hole.png Ac6ve Site of Chymotrypsin with Substrate •  Other Amino acids •  (2) Ile 16 (α- amino): cri6cal ionic interac6on with Asp194 Could you draw a representa6on of ALL of these interac6ons? Cataly3c Triad Ser195 Gly193 Occurs with S binding Asp194 His57 Asp102 VV Fig. 15- 21 Ile16 Salt bridge stabilizes ac3ve conforma3on of the enzyme Ac6ve Site of Chymotrypsin Relevant Amino Acids: MUST KNOW FOR EXAM II •  Cataly3c triad •  Ser195: nucleophile for covalent catalysis •  His57: general acid/base catalysis •  Asp102: strong H- bond (LBHB) increases His57 pK to > 12 in ES complex •  Other Amino acids •  Gly193/Ser195: oxyanion hole •  Ile 16 (α- amino): cri6cal ionic interac6on with Asp194 So what might happen with muta6on of ANY of these...
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