Studies on DMSOR. A Theoretical Approach

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Studies on DMSOR. A Theoretical Approach

• Elizabeth Hernandez-Marin
• October 2, 2009

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Introduction

• 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

• Molybdoenzymes. Generalities

• Functionally, they catalyze a net oxygen atom
  transfer
• X H2O XO 2H 2e-

P. Basu, J. F. Stolz, M. T. Smith, Current
Science, (2003) 84 1412.
3
Introduction

• Can be classified into 3 families represented
  by xanthine oxidase (XO), sulfite oxidase (SO)
  and DMSO reductase (DMSOR)

• Molybdoenzymes. Generalities

XO RCHO ? RCOOH
SO SO32- ? SO42
DMSOR (H3C)2SO ? (H3C)2S
P. Basu, J. F. Stolz, M. T. Smith, Current
Science, (2003) 84 1412.
4
Introduction

• Reaction catalyzed by DMSOR

(CH3)2SO 2H 2e- ? (CH3)2S H2O MoIV ?
MoVI 2e-
N. Cobb, et. al, J. Biol. Chem. (2007), 282,
35519
5
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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Results

• Energy Profile. Mo(OMe)(S2C2H2)2-

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MoIV DMSO
20
10
Kcal/mol
0
-10
?H298
?G298
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Results

• Comparison with actual enzyme

Kinetics studies1 E DMSO ? M ? ES ?
E DMS
Process ?H? kcal/mol ?G? 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
Free energy of formation
Mo(OMe)(S2C2H2)2- DMSO ? I ?
Mo(OMe)(S2C2H2)2- DMSO
1N. Cobb, T. Conrads, R. Hille J. Biol. Chem.
(2005), 280, 3572
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Results

• Comparison 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 Parameters

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Results

• EPR Parameters

g ge ?g
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Results

• MCD spectra for DMSOR and calculated

1M. Seth, T. Ziegler and J. Autschbach J. Chem.
Phys. (2008), 129, 104105
2.80
107.6
Mo
H
S
C
O
N
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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 MoV 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 MoV-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 (e5)

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..
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MCD. Calculation of the C-parameter

• Magnetic Circular Dichroism

E. Hernandez-Marin, M. Seth, T. Ziegler Inorg.
Chem. (2009) 48, 2880.
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