Transcript 5slidesbioinorganic

Essential Metals in Biology
Macro- and micronutrients
Problems to overcome:
Lack of bioavailability
This soup is too cold…
Too much of a good thing
This soup is too hot…
Wilson’s disease: Cu
Accumulation in the eye
Sea
water
(µM)
Blood
plasma
(µM)
Fe
0.001
22
Zn
0.01
17
Cu
0.004
8-24
Ni
0.008
0.04
Co
0.00002 0.000025
Data adapted from Biological
Inorganic Chemistry, Bertini, Gray,
Stiefel, & Valentine, 2007
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This soup is just right…
Getting it “just right”:
Transport and Storage: Iron
Iron scavengers- collecting iron from the environment
•Siderophores – Nature’s fabulous chelator
Getting around
•Transferrin – the Fe transport protein
Long- term storage (or short)
•Ferritin – the Fe storage protein
All of this trouble… begs the question, “why bother?”
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Acid/Base Chemistry
Activating Water to Make Potent Nucleophiles
HCO3-
OH2
Zn2+
His
His
His
H+
H2O
O
O-
-OH
Zn2+
OH
Zn2+
His
His
His
His
O
C
O
CO2
-OH
Zn2+
His
Figure generated from PDB file 1ZNC using Protein Workshop
His
His
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His
His
Oxidation/Reduction Chemistry
A Large Variety of Redox Potentials
(cys)S
S(cys)
(cys)S
(cys)S
(cys)S
Fe
Scys
S
Fe
Fe
(cys)S
S
S(cys)
Fe
S
S
Fe
S(cys)
S
S(cys)
Fe
(cys)S
Fe
S
(cys)S
S
Fe
Fe
S
N(his)
N(his)
S(cys)
(cys)S
Rubredoxin
Fe(III)/Fe(II)
+50 – -50 mV
Ferredoxin
Fe(III)2/Fe(III)Fe(II)
-240 – -420 mV
(HiPIP, +400 – +225 mV)
Ferredoxin
Fe(III)3Fe(II)/
Fe(III)2Fe(II)2/
Fe(III)Fe(II)3
-300 – -600 mV
Rieske iron center
Fe(III)2/Fe(III)Fe(II)
+300 – +150 mV
eS(met)
N(his)
Fe
Fe
N(his)
N(his)
Cytochrome c
Fe(III)/Fe(II)
+260 mV
Cytochrome b
Fe(III)/Fe(II)
+60 mV
Potentials vs. NHE
Me
Me
Me
Me
Me
Me
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Structural Roles for Metals
What can metals get you that carbon can’t ?
•Ability to exceed octet
•Flexibility /Lability of
structure
S-Cys
S
Cys-S
Fe
Fe
S
Fe
S
•Scaffolding for Protein folding
S
Fe
S-Cys
Cys-S
Fe
S
S
Fe
S
Fe
Fe S
Cys-S
S-Cys
sugar
O
His-N
O
Mo
S
Fe
S
Fe
S
Fe
N
S
N
Fe
S
S
S
Fe
S
Fe
S
Fe
S-Cys
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