Notes Lecture 3

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


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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


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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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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


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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)


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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


8/17

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


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NAD+

FADmitochondrial

matrix

inner mitochondrial

membrane

O2

e

e

e

e

e

e


11/17

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


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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


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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


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Dependence of electron transfer barrier on r

E a= a ctivat ionbarrier

r r


r


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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Notes Lecture 3

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