"The Nitrile Hydratase Project"
Many interesting questions/comments were raised in our discussion of the Nitrile Hydratase Model Compound Paper ("First {Fe-NO}6 Complex with an N2S3Fe-NO Core as a Model of NO-Inactivated Iron-Containing Nitrile Hydratase. Are Thiolates and Thioethers Equivalent Donors in Low-Spin Iron Complexes?, Inorganic Chemistry, 2002, 41, 1039).
There is another paper on the same topic in the recent literature (Dey, A.; Chow, M.; Taniguchi, K.; Lugo-Mas, P.; Davin, S. D.; Maeda, M.; *Kovacs, J. A.; *Odaka, M.; *Hedman, B.; *Hodgson, K. O.; *Solomon, E. I. " S K-edge XAS and DFT Calculations on Nitrile Hydratase: Geometric and Electronic Structure of the Non-Heme Iron Active Site," J. Am. Chem. Soc. 2005, 127, 0000 (in press). )
Download the two papers from the libray's website. Read the papers as background for the computational studies.
Questions/Comments raised in class :
(1) The authors claim that their model compound "mimics" the spectroscopy of Nitrile Hydratase.
(2) The authors make the following statement " In summary, thiolates may be substituted by thioethers in ow-spin iron complexes without compromising the integrity of structural models of thiolato-ligated metalloproteins." Can we test this claim by comparing the molecular orbitals of the "model" compound with a model where the thiolate donors have been replaced by thioether?
(3) How many thiolate/thioether donors are needed for there to be similarities between the model compounds and the Nitrile Hydratase?
MOLECULAR ORBITAL CALCULATIONS
NOTE : ALL SPARTAN CALCULATIONS SHOULD BE PERFORMED AT THE PM3 LEVEL. BE SURE TO ENTER THE CORRECT CHARGE AND SPIN MULTIPLICITY FOR YOUR COMPOUND. Calculate and SAVE THE HOMO-4 to LUMO+4 surfaces. Set-up the calculation as shown below:
Create a PLOT in EXCEL of the energies of the HOMO-4 to LUMO+4 orbitals. Past the pictures of each orbital on the graph alongside its energy.
TOPICS
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The
Active Site
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Model
Compounds
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Thiolate
or Thioether?
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 |
 |
 |
| Team A : Natalie
and Vanessa
(1) Background on Nitrile Hydratase - Structure of active site and its function. (2) Download (as a pdb file) the x-ray structure of Nitrile Hydratase (NO bound, inactive form) [ pbd code no. = 1AHJ ] from the Protein Databank (link below). Open the file with Spartan and display the sturucture (model menu) as ribbons, ball and stick and as tubes. Save the view that show the overall structure of the protein the best. (3) Locate the position of the active site. Delete "most" of the protein backbone. Leave only the residues that are attached to the iron. DO NOT MINIMIZE THE ENERGY. The 3-d stucture of the active site from the x-ray data is what we out calculations performed on. Save a view of the active site. (4) Perform the Spartan calculation on the active site. COMPARE YOUR RESULTS WITH THOSE FROM Team B, C, and D.
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Team B : Jim and Lou Perform the molecular orbital calculations on the complex presented in the first paper. (1) From the supporting infomation, download and save the x-ray structure of the complex as a cif (crystal information file)( available for download from the journals website). Open the file with Spartan and display as ball and stick and as tubes (model menu). DO NOT MINIMIZE THE ENERGY. COMPARE YOUR RESULTS WITH THOSE FROM Team A, C, and D. Team C: Jay and Andrea Perform the molecular orbital calculations on a "modified" version of the complex presented in the first paper. (1) From the supporting infomation, download and save the x-ray structure of the complex as a cif (crystal information file)( available for download from the journals website). Open the file with Spartan and display as ball and stick and as tubes (model menu). DO NOT MINIMIZE THE ENERGY. Simply add a methyl group to one of the thiolate sulfur atoms. COMPARE YOUR RESULTS WITH Team A, B and D. Team D: Kat and Jeff
Perform the molecular orbital calculations on a "modified" version of the complex presented in the first paper. (1) From the supporting infomation, download and save the x-ray structure of the complex as a cif (crystal information file)( available for download from the journals website). Open the file with Spartan and display as ball and stick and as tubes (model menu). DO NOT MINIMIZE THE ENERGY. Simply add a methyl group to each of the thiolate sulfur atoms. COMPARE YOUR RESULTS WITH Team B,C, and A
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Team E: Amber, Emir and Bill (1) Try and answer the question " Are Thiolates and Thioethers Equivalent Donors?" by performing MO calculations on : [Fe(S-2)6]10- (Low-spin). (2) Repeat the MO calculation, this time on : [Fe(S)6]3+ sulfur is the coordinating atom in (1) and (2) (3) The authors' in paper 1 propose a reason why thiolate and thioether act the same on Fe(II). Read paper (1) to see the authors' hypothesis. Are the results from (1) and (2) consistent witth the explaination detailed in paper(1)? Support your answer with Molecular Orbital pictures. Are there similarities between your results and those determined by Teams B, C, D. |
| GUIDE TO THE MOLECULAR ORBITALS OF METAL COMPLEXES |
Links
The Kovac's Research Group - Snythetic Models for Nitrile Hydratase
The Nitrile Hydratase Page at the Center for Protein Structure and Function
