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Substrate Pathways in the Nitrogenase MoFe Protein by Experimental Identification of Small Molecule Binding Sites

Morrison, Christine N. and Hoy, Julie A. and Zhang, Limei and Einsle, Oliver and Rees, Douglas C. (2015) Substrate Pathways in the Nitrogenase MoFe Protein by Experimental Identification of Small Molecule Binding Sites. Biochemistry, 54 (11). pp. 2052-2060. ISSN 0006-2960. PMCID PMC4590346.

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In the nitrogenase molybdenum-iron (MoFe) protein, we have identified five potential substrate access pathways from the protein surface to the FeMo-cofactor (the active site) or the P-cluster using experimental structures of Xe pressurized into MoFe protein crystals from Azotobacter vinelandii and Clostridium pasteurianum. Additionally, all published structures of the MoFe protein, including those from Klebsiella pneumoniae, were analyzed for the presence of nonwater, small molecules bound to the protein interior. Each pathway is based on identification of plausible routes from buried small molecule binding sites to both the protein surface and a metallocluster. Of these five pathways, two have been previously suggested as substrate access pathways. While the small molecule binding sites are not conserved among the three species of MoFe protein, residues lining the pathways are generally conserved, indicating that the proposed pathways may be accessible in all three species. These observations imply that there is unlikely a unique pathway utilized for substrate access from the protein surface to the active site; however, there may be preferred pathways such as those described here.

Item Type:Article
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URLURL TypeDescription Information CentralArticle
Morrison, Christine N.0000-0002-4180-8407
Rees, Douglas C.0000-0003-4073-1185
Additional Information:© 2015 American Chemical Society. ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Received: October 20, 2014. Revised: February 18, 2015. Publication Date (Web): February 24, 2015. Funding: This material is based upon work supported by the National Science Foundation Graduate Research Fellowship (Grant DGE-1144469 to C.N.M.), the National Institute of Health (NIH Grant GM45162 to D.C.R.), the Howard Hughes Medical Institute (to D.C.R.), the European Research Council (Grant 310656 to O. E.), and Deutsche Forschungsgemeinschaft (Grants Ei-520/7 and IRTG 1478 to O.E.). We acknowledge the Gordon and Betty Moore Foundation, the Beckman Institute, and the Sanofi-Aventis Bioengineering Research Program at Caltech for their generous support of the Molecular Observatory at Caltech. We thank the staff at Beamline 12-2, Stanford Synchrotron Radiation Lightsource (SSRL), operated for the DOE and supported by its OBER and by the NIH, NIGMS (P41GM103393), and the NCRR (P41RR001209). We thank Jens Kaiser and James Howard for helpful discussions as well as Thomas Spatzal for discussions and his assistance with the xenon pressurization. Accession Codes: The structural model and structure factors have been deposited with the Protein Data Bank. The PDB ID for the Av1-Xe and Cp1-Xe structures are 4WNA and 4WN9, respectively.
Funding AgencyGrant Number
NSF Graduate Research FellowshipDGE-1144469
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
European Research Council (ERC)310656
Deutsche Forschungsgemeinschaft (DFG)Ei-520/7
Deutsche Forschungsgemeinschaft (DFG)IRTG 1478
Gordon and Betty Moore FoundationUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Caltech Sanofi-Aventis Bioengineering Research ProgramUNSPECIFIED
Issue or Number:11
PubMed Central ID:PMC4590346
Record Number:CaltechAUTHORS:20150317-100736214
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Official Citation:Substrate Pathways in the Nitrogenase MoFe Protein by Experimental Identification of Small Molecule Binding Sites Christine N. Morrison, Julie A. Hoy, Limei Zhang, Oliver Einsle, and Douglas C. Rees Biochemistry 2015 54 (11), 2052-2060 DOI: 10.1021/bi501313k
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55843
Deposited By: Ruth Sustaita
Deposited On:17 Mar 2015 17:40
Last Modified:09 Mar 2020 13:19

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