Mechanisms
of
enzyme
catalysis
Acid-base
→
Gives
/
takes
protons
Amino
acid
General
acid
form
Genera
/
base
form
residues
(
proton
donor
)
(
proton
acceptor
)
↑
'
R3
Reactant
species
H
-
C
,
-0
+
4=0
Glu
,Asp
R
-
COOH
R
-
COO
-
R2
N
-
H
H
£4
Without
catalysts
,
Lys
,Arg
BINH
R
-
Nitz
11
unstable
/
charged
H
intermediate
breaks
,
µ
,
down
rapidly
;
forms
Cys
R
-
SH
R
-
S
-
When
proton
transfer
µ
_
{
[
-
{
[
◦
-
reactants
to
/
from
H2O
-
Faster
R
_,C=CH
R
-
,C=CH
than
the
rate
of
R2
N
-
H
break
-
down
of
When
proton
transfer
It
\
intermediates
;
OH
-
£4
B
:
toorfromtlzois
slower
His
HN\yNH
HN
#
N
:
presence
of
other
+1201-1-1
A
than
the
rate
of
break
-
proton
donors
or
down
of
intermediates
,
H
µ
only
a
fraction
of
the
acceptors
does
not
§
+
intermediates
formed
Ser
R
-
OH
R
-
O
-
increase
rate
of
HOH
<
>
BH
]
✗
µ
,
a
,
,,a
,
,
,
,
,
@
g.
µ
,
reaction
HOH
presence
of
alternative
proton
donors
/
HA
>
or
Tyr
R--
OH
R-\_
0
-
ppl
R3
acceptors
CB
:)
increases
the
rate
of
reaction
4-
f-
0-4-0
-
R2
H
-
NIH
'
ra
covalent
→
Change
reaction
paths
t
R
'
R
}
1
"
it
"
Transient
bond
between
the
enzyme
+
substrate
Products
1-1-4-01=0-1
N
,
R2
R4
↳
serine
proteases
→
acyl
-
serine
intermediate
Metal
10h
→
Redox
cofactors
,
pKa
shifters
cysteine
proteases
→
acyl
-
eystein
intermediate
protein
kinases
+
phosphates
→
phospho
-
amino
acid
intermediate
-
Binding
substrates
in
proper
orientation
(
e.
g.
cytochromes
)
pyridoxal
-
cont
'g
enzymes
→
lysine
-1111-12
;
Schiff
bases
-
Mediating
oxidation
-
reduction
reactions
changes
direct
pathway
-
Electrostatically
stabilizing
/
Shielding
negative
charges
that
would
otherwise
repel
the
attack
from
an
electrophile
↳
uncatlyzed
→
A-
B.
"
"
AB
+1,0
l
electrostatic
)
catalyzed
(
✗
=
catalyst
>
→
A-
B
X
:
A
-
✗
B
A
×
:
Electrostatic
->-
Charge
-
Metallo
enzymes
contain
tightly
bound
metal
Requires
a
nucleophile
on
the
enzyme
10ns
:
fet2-e-3.cat?zn+2
↳
Donation
of
electrons
from
enzyme
nucleophile
-10
substrate
-
Metal
-
activated
enzymes
contain
loosely
side
chains
of
His
,
Cys
,Asp
,
Lys
,
and
Ser
can
participate
in
bound
metal
10ns
(
Nat
,KIMg+
}
orca
-12
covalent
catalysis
by
acting
as
nucleophiles
Chymotrypsin
Mechanism
Chymotrypsin
step
/
→
substrate
binding
Digestion
→
Dietary
proteins
broken
down
into
small
peptides
by
proteases
substrate
binds
,
-
side
chain
of
residue
adjacent
-10
the
peptide
bond
-10
be
cleared
nestles
/
na
Enzyme
substrate
complex
chymotrypsin
lfreeenzymelhydropnobicpockec-ion-neenzy.me
One
of
several
proteases
that
cuts
peptides
at
specific
locations
on
peptide
backbone
.gg/(ASPposH10nthg-hepep-1debondfora+tacKAc+ivesi-e
"JYH
#
,
-1,4¥
¥~H
Able
-10
Cleave
the
peptide
bond
adjacent
-10
aromatic
amino
acids
hole
substrate
/
a-
polypeptide
)
←
Hiv
,
%
AA-E.IE#-Y-y-*-E.-g-aa
.
"
"
"
"
%
"
Hydrophobic
,¥
,
④
Chymotrypsin
cuts
bond
pocket
step
2
→
Nucleophilic
attack
/
CY
}fHs
CH
Interaction
of
Ser
"¥nd
Hiss
>
generates
a
strong
nucleophilic
alkoxide
Lonon
Seri
short-lived
intermediate
CHZOH
,H
1H
CHZ
[
H2
"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
"
+%ʰ¥YM.:ÉÑ*ÉÉ*
%É¥ÉÉÉ?¥¥%
Substrate
group
.
forming
a
tetrahedral
acyl
C.
acylation
)
I
complex
enzyme
accompanied
by
formation
of
HÑ-¥
-
g-
Ny
,
-
g-
N'
"
¥
__¥
-1¥
,
Too
-
a
short
-
lived
C-
)
I
11
TF
charge
on
the
carbonyl
H
{
'
"
]VHis
oxygen
otthe
substrate
:
THIS
Aa
-
%
!
-
did
N
Amino-terminal
end
.
bonding
in
the
s-iabinzedbsmdr%fa-II-i-i.FI
,
¥+1
-
E-
a
"
1¥
-
µµ_d%
-
E-
AA
oxyanionhole
"
i%¥ser
-
H"É÷¥+¥ser
É¥
2
-
¥
-
Gly
