Post on 08-Apr-2018
8/7/2019 Notes Lecture 3
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SN
SOO
M
M
Metalloenzymes
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placed in an environment where
its selected function is: kinetically favored
thermodynamically favored
+n
Function of Metal Ions in Biology:
1. electron transport/transfer
2. small molecule/atom transport/transfer
3. bind and activate substrates4. stabilize a protein structure
8/7/2019 Notes Lecture 3
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e transport/transfer
bind and activate
substrates
single atom transfer
stabilize a protein
structure
Metal Ion Requirements
small reorganizational barrier
appropriate redox potential
"vacant" binding site
filledd orbitals, or,
Lewis acidic charactor
"vacant" binding site
appropriate redox potential
non-redox active metal ion
large Keq (M+n + protein)
Function
8/7/2019 Notes Lecture 3
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Weve seen that metal ions have very different properties
How is it that metal ions can be used interchangeably?
e.g., Cu vs.Fe in electron transfer, Fe vs. Mn vs.Cu insuperoxide disproportionation, etc.
How is it that Fe can be used for different functions?
(as well as Cu, Zn, Mn, Ni, V, Mo, )
Answer: the properties of metal ions can be tuned
by altering its ligands
by altering its geometry by altering nearby residues
(e.g., H-bonding, polarity, etc.)
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8/7/2019 Notes Lecture 3
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SN
SOO
M
NH
Protein: can donateprotons, Hbonds, etc
Metal Ion:
catalyzes rxns
Protein: can constrain the metal
ion geometry in a near
transitionstate = ENTATICSTATE
Protein:responsible for
selectivity in
substrate binding
Protein: usually creates a
hydrophobic pocket =
nature's organic solvent
Protein: tunes
the metal ion's
properties
Metal Ion
+ ligated
atoms= the
"ACTIVE
SITE"
Metalloenzyme Active Sites
are Finely Tuned to Favora Selected Function
8/7/2019 Notes Lecture 3
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[Co(H2O)6]+2
e
e
[Co(H2O)6]+3
[Co(EDTA)3]2 [Co(EDTA)3]
E1/2= 0.60 V
E1/2= 1.84 V
e
e
[Co(en)3]+2 [Co(en)3]
+3E1/2= +0.26 V
e
e
[Co(NH3)6]+2
e
e
[Co(NH3)6]+3 E1/2= 0.10V
[Co(CN)5]3
e
e
[Co(CN)6]3 E1/2= +0.83 VCN+
Influence of Ligand on Redox Potentials
(Thermodynamics)
8/7/2019 Notes Lecture 3
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[Cu(Osal)2en] 1.21 V
E1/2
Cu(Mesal)2 0.90 V
Cu(Etsal)2 0.86 V
Cu(iPrsal)2 0.74 V
[Cu(Ssal)2en] 0.83 V
Cu(tBusal)2 0.66 V
Influence of Ligating Atoms andGeometry on Redox Potentials
O
N
R
Cu
O
N
R
Cu(Rsal)2
Cu
X
N
X
N
[Cu(Xsal)2en]
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Redox Potentials of ElectronTransport Sites Found in Biology
Nhis CuScysNhisS
met
blue copper
+2
cyt c
Fe
Smet
Nhis
E1/2= +370 mV E1/2= +260 mV
+2
cyt b
Fe
Nhis
Nhis
E1/2= +60 mV
Scys
ScysFe Scys
Scys
rubredoxinE1/2= 60 mV
Fe S
FeSFe
S Fe
S
Scys
Scys
Scys
Scys
3
ferredoxin
FeSS
FeS
cys
ScysScys
Scys
ferredoxin
2
E1/2= 430 mV E1/2= 400 mV
1
8/7/2019 Notes Lecture 3
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N N
Electron Transfer Reactions
M+n
ne
CO2
....one of the most important reactions inbiology!
6e, 6H+
CO + H2O
substrate
O O
2 NH3
4e, 4H+2 H2O
2e, 2H+
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ferredoxin
NADH
FAD
Cytochrome b
Cytochrome c1
Cytochrome c
Cytochrome c oxidase
O2
400
E1/2
+800 (+815 mV)
+500
+300
0.0 (+60 mV)
(320 mV)
(+260 mV)
E
Besides promoting redox reactions,
electron transfer is intimately connected
with energy storage in mitochondria (as
ATP), via the electrontransport chain
G= 52.6 kcal/mol
8/7/2019 Notes Lecture 3
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NAD+
FADmitochondrial
matrix
inner mitochondrial
membrane
O2
e
e
e
e
e
e
8/7/2019 Notes Lecture 3
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Redox Potentials of ElectronTransport Sites Found in Biology
Nhis CuScysNhisS
met
blue copper
+2
cyt c
Fe
Smet
Nhis
E1/2= +370 mV E1/2= +260 mV
+2
cyt b
Fe
Nhis
Nhis
E1/2= +60 mV
Scys
ScysFe Scys
Scys
rubredoxinE1/2= 60 mV
Fe S
FeS
Fe
S Fe
S
Scys
Scys
Scys
Scys
3
ferredoxin
FeSS
FeS
cys
ScysScys
Scys
ferredoxin
2
E1/2= 430 mV E1/2= 400 mV
1
8/7/2019 Notes Lecture 3
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M+n
e
electrode surface
....studied in the lab under m ore
cont rolled condit ions...
Thermodynamics
ie, energy of e delivered
*
M+n
e
Kinetics
ie, rate of e
transfer
Chapter 7
8/7/2019 Notes Lecture 3
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example
[Cr(II)L6]+2 + [Cr(III)L6]
+3
e
[Cr(III)L6]+3 +
Potential Well descriptionof the Barrier to e transfer
[Cr(II)L6]+2
Kinetics
Selfexchange Reaction
G= 0, M1= M2
r= total changein CrL distance
conversion
required for
Cr+2> Cr+3
r/2= change
in CrL distance
e transferrequired for
E
r
r /2
Ea= activationbarrier
increasingML distance
Ea= activation
barrier
8/7/2019 Notes Lecture 3
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Dependence of electron transfer barrier on r
E a= a ctivat ionbarrier
r r
E a= a ctivat ionbarrier
r
E a= a ctivat ionbarrier
Conclude: Ratesare proportional
to r
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M2
+2
r ed u ce d p r od u ct
activation
stepM2
+3
a c t i v a t e d
com p lex
e
e transferM2
+3
oxid ized
M2 Llong
groun d sta te for M2+n
+(n1)M2 L
elongated
vibrationally excited
+n
sta te for M2+n
M2 L
short
groun d sta te for M2+(n1)
+n
e
a c c e p t o r
Frank Condon principleFrank Condon principle
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Fe S
FeS
Fe
S Fe
S
SR
RS
RS
SR
Fe S
FeS
Fe
S Fe
S
SR
RS
RS
SR
2 3
e
e
+2.5 +2.25
e
Fe4S4 Clusters in Biology
added electron is
delocalized over
all four Fe ions !
thus, the charge on each
iron changes by only 1/4 of
a unit, rather than one full
charge unit!
this minimizes
the barrier to
electron transfer
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