Lecture 18 Flashcards
Enzyme reaction mechanisms
nucleoplilic
a atom or molecule who is electron rich and wants to donate electrons
electrophilic
a atom or molecule that is electron poor and wants to donate electrons.
electropositive
is what happens to an atom becomes electron deficient (the nucleophiles goal)
electronegative
is what happens to an atom that becomes electron rich (the electrophile’s goal)
Electron pushing
the direction on the nucleophilic attack. the electrons on the electronegative nucleophile with attack the electropositive electrophile
Base catalysis
When the histidine takes a proton from a serine and water making them now act like nucleophililes
Covalent catalysis
when serine get deprotonated (nucleophiles) it attacks electron deficient (electrophiles) atoms so they can form covalent intermediates
which comes first, base catalysis or covalent catalysis
Base catalyst comes first as they histide takes away a proton from the serine so it becomes deprotroned and electronegative. Its now a nucleophile so it attacks the electron deficient atoms to form covalent intermediates
What are serine proteases?
They are enzymes that cleave peptide bond in proteins
Chymotrypsin
a type of serine protease that cleaves peptide bonds at C and N terminus by having a protein specificity for tryptophan, methionine, phenylalanine, tyrosine
Substrate specificity pocket
Where the enzyme detects specific amino acid to know where to cut the peptide bond
active site of the serine process
is where catalytic triad of ser195, his157 and asp102 reside
What is Serine195’ job?
Covalent Catalysis- after being deprotonated it now acts as a nucleophile and must create a covalent intermediate with the substate (polypeptide)
What is Histidine57 job?
Base Catalysis - must deprotonate Ser195 so it can act like a nucleophile
What is Asp102 job?
it must stabilizes His57 anytime it becomes protonated.
Explain the chymotrypsin reaction mechanism process
1) a polypeptide will go through substrate specificity pocket until the desired peptide is detected
2) Base catalysis of Ser195 from His57 and covalent catalysis of the carbonyl carbon of the polypeptide by the nucleophilic Ser195
3) The His57 gives the proton to the N terminus of the animo acid (substrate) causing the bond between the tetrahedral Carbonyl carbon to break as nitrogen is the best leaving group, now product 1 is free
4) The serine is now bonded to the other half of the substrate with the specific amino group forming an acyl-enzyme intermediate.
5) Water comes and the his57 again takes a proton from it causing it to become a nucleophile. It attacks the carbonyl of the acyl enzyme intermediate
6) His57 returns proton to Ser195 allowing it to cleave from the substrate and the second product is formed.
Enzyme is now reset and ready to do it again
Oxyanion hole
a place of positive dipole so negative charge can be stabilized while the breaking of bonds
scissile bond
the peptide bond that is cleaved to make first product
where is the polypeptide cleaved?
in between the c and n terminus after the specific animo acid is detected.
