Catalytic Strategies Flashcards
what are the 6 catalytic strategies an enzyme can use?
- preferential transition state binding
- proximity and orientation effects
- general acid base catalysis
- covalent catalysis
- electrostatic catalysis
- metal ion catalysis
amino acid side chains are the main determinants of enzyme __ and __
structure and function
the active site of an enzyme has what 2 types of residues?
those that form bonds with the substrate and those that catlyse
what type of amino acids have the most important roles in the active site>
polar, especially if ionizable
what are catalytic amino acids?
play a direct role in catalysis
“cation and anion binding” and “hydrogen bonding” indicates what type of role in the active site?
accessory
“proton transfer” and “covalent binding” indicates what type of role in the active site?
catalytic
what are the various roles of polar amino acids? (3)
- proton transfer
- transient covalent bonds to substrate
- substrate and TS bonding through charge–chrage interactions
why is histidine such a common catalytic residue?
side chain pka 6-7 (close to physiological pH), both protonated and unprotonated form will be present and it can therefore accept or donate protons
what is preferential transition state binding?
catalytic strategy where the enzyme binds better to the TS than the substrate of products
in preferential TS binding, the max binding energy is released when?
at the TS
how does preferential TS binding increase reaction rate?
the enzyme strains the substrate to the TS shape, possibly bringing reacting groups closer together
what are TS analogues?
stable molecules that bind strongly to enzymes because the mimic the TS shape
why are TS analogues bad for reaction progression?
they can’t become products, so the enzyme is stuck and inhibited from turning actual TS to products
TS analogues are an example of what type of inhibition?
competitive
HIV has 3 main replication enzymes
- reverse transcriptase
- integrase
- protease
what is the function of reverse transcriptase?
turns viral RNA into dsDNA
what is the function of intergrase?
inserts viral genome into host chromosomes
what is the function of protease>
processes viral proteins so they can assemble into new viruses
proximity effect in single substrate reactions
the substrate molecule may be contorted to bring the reacting functional groups to clover together
proximity effect in multi-substrate reactions
binding of substrate to enzyme increases their local or effective concentration
orientation effect
enzymes orient reacting molecules to promote reaction
what is the most common ( not most important) catalytic strategy?
general acid base catalysis
general acid-base catalysis relies on amino acid side chains that can ___
donate and accept a proton
what is the goal of acid base catalysis?
lower the free energy of TS
a general acid __ an H to an atom that develops a __ charge in the TS
donates ; negative
a general base ___ an H to an atom that develops a ___ charge in the TS
accepts ; positive
what is covalent catalysis (catalytic strategy?
a side chain with a nucleophilic group makes a transient bond with an electrophilic group on the substrate
in covalent catalysis, what changes about the reaction pathway?
there is an extra intermediate state
what does the intermediate state in covalent catalysis look like?
similar to TS but lower free energy
what is the effect of the extra intermediate in covalent catalysis?
lowers the overall free energy of the TS
what amino acids can act as nucleophiles?
serine, cysteine, aspartate and glutamate
some proteases (like chymotrypsin) use serine to __
hydrolyze peptide bonds in their proteins
role of chymotrypsin in the body
Diest proefins in the small intestine
T/F chymotrypsin, trypsin, and elastase come from a common ancestor
t
chymotrypsin, trypsin, and elastase have the same substrate and cleavage site preferences
f
chymotrypsin selectively cleaves the peptide bond at the __ side of large __ amino acids
carboxyl-terminal; hydrophobic
chymotrypsin is composed of __ different polypeptides held together by ___ bonds
3; disulphide
what acts as the nucleophile in chymotrypsin?
serine residue
chymotriopsin is known as a __ because it is made of 3 catalytic amino acids in its active site
catalytic triad
what part of chymotrypsin its as the general base?
HIS 57
