studies on dmsor. a theoretical approach elizabeth hernandez-marin october 2, 2009

Studies on DMSOR. A Theoretical Approach

Elizabeth Hernandez-Marin

October 2, 2009

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.

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

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-

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

-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

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

Results Com

parison with actual enzyme

Enzyme: E + DMSO → M → ES → E’ + DMS

Calculated: [MoIV] + DMSO → I → [MoVI] + DMSO

Yellow: enzyme. Green: optimized structure.

Results EPR Param

eters

Results EPR Param

eters

g= ge + Δg

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

Contributions to C-terms

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.

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

…..

€

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