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Studies on DMSOR. A Theoretical Approach
Elizabeth Hernandez-Marin
October 2, 2009
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Introduction M
olybdoenzymes. Generalities
Molybdenum is the only 4d transition metal required for all forms of life. Generally found as mononuclear active centers.The metal ion is coordinated by a modified pyranopterin cofactor:
Functionally, they catalyze a net oxygen atom transfer:
X + H2O = XO + 2H+ + 2e-
N
H
N
N
H
N
H
O
N
H
2
O
S
H
S
H
R
P. Basu, J. F. Stolz, M. T. Smith, Current Science, (2003) 84 1412.
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Introduction M
olybdoenzymes. Generalities
Can be classified into 3 families represented by xanthine oxidase (XO), sulfite oxidase (SO) and DMSO reductase (DMSOR)
P. Basu, J. F. Stolz, M. T. Smith, Current Science, (2003) 84 1412.
S
Mo
O
H
O
H
S
S
Mo
O
S
S
S
S
(
S
e
r
)
O
O
Mo
O
(
C
y
s
)
S
S
S
XO : RCHO → RCOOH
SO: SO32- → SO4
2
DMSOR: (H3C)2SO → (H3C)2S
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Introduction Reaction catalyzed by DM
SOR
N. Cobb, et. al, J. Biol. Chem. (2007), 282, 35519
(CH3)2SO + 2H+ + 2e- → (CH3)2S + H2O
[MoIV] → [MoVI] + 2e-
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Introduction
S. Bailey, A. McAlpine, E.M.H. Duke, N. Benson, A. McEwan, Acta Cryst. 1996, D52, 194 A. McAlpine, A. McEwan, S. Bailey J. Mol. Biol 1998, 275, 613
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-13.2MoVI
+DMS
-12.3
Results
Energy Profile. [Mo(OM
e)(S2C2H2)2]-
0
10
20
-10
Kcal
/mol
G298
H298
MoIV
+DMSO
26.4
9.0
3028.7
16.6
8.1
23.9
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Results Com
parison with actual enzyme
Process ΔH≠
kcal/molΔG≠
Kcal/mol
Experimental1
[MoIV] + DMSO → M -5.0*
M → ES nd 13.0
ES → E’ + DMS 15.6 15.0
Calculated [MoIV] + DMSO → I 9.0 26.4
I → [MoIV] + DMS 8.5 4.8
Kinetics studies1: E + DMSO → M → ES → E’ + DMS
[Mo(OMe)(S2C2H2)2]- + DMSO → I → [Mo(OMe)(S2C2H2)2]- + DMSO
* Free energy of formation
1N. Cobb, T. Conrads, R. Hille J. Biol. Chem. (2005), 280, 3572
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Results Com
parison with actual enzyme
Enzyme: E + DMSO → M → ES → E’ + DMS
Calculated: [MoIV] + DMSO → I → [MoVI] + DMSO
Yellow: enzyme. Green: optimized structure.
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Results EPR Param
eters
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Results EPR Param
eters
g= ge + Δg
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Mo H
C O N
107.6°
S
2.80
Results
MCD spectra for DM
SOR and calculated
€
CJ = − 4i3G
M2
M∑ εαβγ A M α J
(1)γJ M β A
(0)
αβγ∑
1M. Seth, T. Ziegler and J. Autschbach J. Chem. Phys. (2008), 129, 104105
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Contributions to C-terms
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Final Remarks
Based on complexes taken from the active site of the molybdoenzyme DMSOR it was possible to:
• Outline a plausible energy profile for the oxidation of DMSO to DMS by the enzyme.
• Explain the physical origin of the EPR parameters of the enzymatic Mo[V] species, due to the good agreement between the calculated and experimental parameters. • Obtained a detailed account of the contributions that made up the MCD spectrum of the Mo[V]-DMSOR in terms of C-parameters.
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Computational Details and models
Calculations performed with ADF. Functional: BP86 Basis set: TZP. Small Core. Default convergence criteria Solvation model: COSMO (ε=5)
Mo
S
S
S
S
O
Mo
S
S
S
S
OCH3
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…..
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€
A Mα J(1)γ
= K '(0) Mα J (0)K '(0) H SO
γ A(0)
EK ' − EA
+ A(0) Mα K (0)
K ≠J∑
J (0) H SOγ K (0)
EK − EJK '≠A∑€
CJ = − 4i3G
M2
M∑ εαβγ A Mα J
(1)γJ M β A
(0)
αβγ∑
E. Hernandez-Marin, M. Seth, T. Ziegler; Inorg. Chem. (2009) 48, 2880.
MCD. Calculation of the C-parameter M
agnetic Circular Dichroism
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