Post on 16-Jan-2016
H2O
CaCO3
C2H5OH
(C650,000 H4,400,000 O1,800,000
N100,000 Na3 Cl3 S2 K1 Ca0.3
Mg0.3 P0.3 Fe0.1 Zn0.1 Cu0.01
Si0.001 Co0.00001 Se0.0000001….)n
Medical Use
Trace Element
Human Carbonic Anhydrase II
Human Carbonic Anhydrase II
Håkansson, K.; Carlsson, M.; Svensson, L. A.; Liljas, A. J. Mol. Biol. 1992, 227(4), 1192.
CO2 + H2O
HCO3– + H+
3 × 108 dm3 mol–1 s–1
The Main Challenges
•Understanding
•Biomimetic Chemistry
•New drugs
0
10
20
30
40
50
60
70
801
97
4
19
85
19
91
19
94
19
95
19
97
RD
I ma
le
RD
Ife
ma
le
Selenium Intake UK / microg d-1
MAFF Food Surveillance Information Sheets 126 and 191
Biomimetic Chemistry
2H+ + 2e- H2 Hydrogenases
CO2 + H2O HCO3- + H+ Hydrases
6CO2 + 6H2O C6H12O6 + 6O2 Photosystems
zinc(II)
His-94His-96 His-119
His-200
Glu-106
Thr-199
O(1)O(2)
O(3)
Liljas, A.; Xue, Y.; Vidgren, J.; Anders Svensson, L.; Jonsson, B. H.; Lindskog, S.; Proteins, 1993, 15, 80
M
O
O
O
q = interplanar angle
plane one
plane two
Active Site Structure of HCA II Thr-200 His Complex with HCO3
–
Complex and Active Site
Zn(1) N(5) = 5.641(2) cf. Zn N(Thr199) = 5.851(4) Å
New Medicines
O2 + e - O2 -
superoxide
2O2 - + 2H+ H2O2 + O2
Superoxide dismutase
IC50 value = 3 x 10-6 mol dm-3
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