Density functional theory study of model complexes for the revised nitrate reductase active site in Desulfovibrio desulfuricans NapA
Abstract
[Mo(SSCH3)(S2C2(CH3)2)2](x) complexes with charges x between -3 and +3 were investigated by density functional theory computations as minimal nitrate reductase active-site models. The strongly reduced species (x = -2, -3) exist preferentially as pentacoordinate sulfo complexes separated from a thiolate anion. The oxidized extremes (x > 0) clearly prefer hexacoordinate complexes with an eta(2)-MeSS ligand. Among the neutral and especially for the singly negatively charged species structures with eta(2)-MeSS and eta(1)-MeSS ligands are energetically close to the sulfo methyl sulfide complex without SS bonding. For x = -1 the three isomers lie in a 1.5 kcal mol(-1) energy range. Putative mechanistic pathways for nitrate reduction from the literature were investigated computationally: (1) reduction at a pentacoordinate sulfo complex, (2) reduction at the ligand, and (3) reduction at the molybdenum center with an R-S-S ligand. All three pathways could be traced at least for some overall charges but no definite conclusion can be drawn about the mechanism. Complexes with larger dithiolato ligands were also computed in order to model the tricyclic metallopterin framework more accurately: the first heterocyclus (5,6-dihydro-2H-pyran) stabilizes the nitrate complex and the molybdenum oxo product complex by approximately 10 kcal mol(-1) and also reduces the activation barrier (by approximately 5 kcal mol(-1)). The effect of the second (1,2,3,4-tetrahydropyrazin) and third heterocyclus (2-amino-3H-pyrimidin-4-one) on the relative energies is relatively small. For bigger models derived from an experimental protein structure, nitrate reduction at a persulfo molybdenum(IV) complex fragment (mechanism 3) is clearly favored over the oxidation of a molybdenum-bound sulfur atom (mechanism 2). Mechanism 1 could not be investigated for the big models but seems the least favorable on the basis of the results from smaller models.
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The mechanistic proposal for the persulfide bond was corroborated by density functional theory calculations.
“The mechanistic proposal was corroborated by density functional theory calculations. 202,203”
From Nitrate and periplasmic nitrate reductases (2014) · cites this paper as [202]
Cites
Density-functional thermochemistry. III. The role of exact exchange
Becke, A. D. (1993) · The Journal of Chemical Physics · doi:10.1063/1.464913 · Cited by 103,767 · see citing works
Lee, C., Yang, W., & Parr, R. G. (1988) · Physical Review B · doi:10.1103/physrevb.37.785 · Cited by 100,874 · see citing works
Density-functional exchange-energy approximation with correct asymptotic behavior
Becke, A. D. (1988) · Physical Review A · doi:10.1103/physreva.38.3098 · Cited by 53,837 · see citing works
Density-functional approximation for the correlation energy of the inhomogeneous electron gas
Perdew, J. P. (1986) · Physical review. B, Condensed matter · doi:10.1103/physrevb.33.8822 · Cited by 18,762 · see citing works
Hay, P. J., & Wadt, W. R. (1985) · The Journal of Chemical Physics · doi:10.1063/1.448975 · Cited by 15,622 · see citing works
Hay, P. J., & Wadt, W. R. (1985) · The Journal of Chemical Physics · doi:10.1063/1.448799 · Cited by 13,834 · see citing works
Barone, V., & Cossi, M. (1998) · The Journal of Physical Chemistry A · doi:10.1021/jp9716997 · Cited by 10,264 · see citing works
Wadt, W. R., & Hay, P. J. (1985) · The Journal of Chemical Physics · doi:10.1063/1.448800 · Cited by 10,092 · see citing works
Klamt, A., & Schüürmann, G. (1993) · Journal of the Chemical Society Perkin Transactions 2 · doi:10.1039/p29930000799 · Cited by 9,449 · see citing works
Energy-adjustedab initio pseudopotentials for the second and third row transition elements
Andrae, D., Häußermann, U., Dolg, M., Stoll, H., & Preu�, H. (1990) · Theoretica Chimica Acta · doi:10.1007/bf01114537 · Cited by 8,561 · see citing works
Cossi, M., Rega, N., Scalmani, G., & Barone, V. (2003) · Journal of Computational Chemistry · doi:10.1002/jcc.10189 · Cited by 8,056 · see citing works
Cell biology and molecular basis of denitrification
Zumft, W. G. (1997) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.61.4.533-616.1997 · Cited by 3,483 · see citing works
The mononuclear molybdenum enzymes
Hille, R., Hall, J., & Basu, P. (2014) · Chemical Reviews · doi:10.1021/cr400443z · Cited by 1,738 · see citing works
The Mononuclear Molybdenum Enzymes
Hille, R. (1996) · Chemical Reviews · doi:10.1021/cr950061t · Cited by 1,501 · see citing works
Optimized density functionals from the extended G2 test set
Schmider, H. L., & Becke, A. D. (1998) · The Journal of Chemical Physics · doi:10.1063/1.476438 · Cited by 752 · see citing works
Insights into the respiratory electron transfer pathway from the structure of nitrate reductase A
Bertero, M. G., Rothery, R. A., Palak, M., Hou, C., Lim, D., Blasco, F., Weiner, J. H., & Strynadka, N. C. J. (2003) · Nature Structural & Molecular Biology · doi:10.1038/nsb969 · Cited by 494 · see citing works
Synthetic Analogues and Reaction Systems Relevant to the Molybdenum and Tungsten Oxotransferases
Enemark, J. H., Cooney, J. J. A., Wang, J., & Holm, R. H. (2003) · Chemical Reviews · doi:10.1021/cr020609d · Cited by 472 · see citing works
Crystal structure of the first dissimilatory nitrate reductase at 1.9 Å solved by MAD methods
Dias, J. M., Than, M. E., Humm, A., Huber, R., Bourenkov, G. P., Bartunik, H. D., Bursakov, S., Calvete, J., Caldeira, J., Carneiro, C., et al. (1999) · Structure · doi:10.1016/s0969-2126(99)80010-0 · Cited by 286 · see citing works
Architecture of NarGH Reveals a Structural Classification of Mo-bisMGD Enzymes
Jormakka, M., Richardson, D. J., Byrne, B., & Iwata, S. (2004) · Structure · doi:10.1016/j.str.2003.11.020 · Cited by 212 · see citing works
Andrae, D., H�u�ermann, U., Dolg, M., Stoll, H., & Preu�, H. (1991) · Theoretical Chemistry Accounts · doi:10.1007/bf01112848 · Cited by 163 · see citing works
Structural and redox plasticity in the heterodimeric periplasmic nitrate reductase
Arnoux, P., Sabaty, M., Alric, J., Frangioni, B., Guigliarelli, B., Adriano, J.-M., & Pignol, D. (2003) · Nature Structural & Molecular Biology · doi:10.1038/nsb994 · Cited by 149 · see citing works
Jepson, B. J. N., Mohan, S., Clarke, T. A., Gates, A. J., Cole, J. A., Butler, C. S., Butt, J. N., Hemmings, A. M., & Richardson, D. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607353200 · Cited by 120 · see citing works
Najmudin, S., González, P. J., Trincão, J., Coelho, C., Mukhopadhyay, A., Cerqueira, N. M. F. S. A., Romão, C. C., Moura, I., Moura, J. J. G., Brondino, C. D., et al. (2008) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-008-0359-6 · Cited by 116 · see citing works
Dithiolene chemistry : synthesis, properties, and applications
Stiefel, E. I. (2004) · Wiley eBooks · Cited by 99 · see citing works
Joshi, H., Cooney, J. J. A., Inscore, F. E., Gruhn, N. E., Lichtenberger, D. L., & Enemark, J. H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0636832100 · Cited by 93 · see citing works
Tuning a Nitrate Reductase for Function
Jepson, B. J. N., Anderson, L. J., Rubio, L. M., Taylor, C. J., Butler, C. S., Flores, E., Herrero, A., Butt, J. N., & Richardson, D. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402669200 · Cited by 79 · see citing works
Leopoldini, M., Russo, N., Toscano, M., Dułak, M., & Wesołowski, T. A. (2006) · Chemistry - A European Journal · doi:10.1002/chem.200500790 · Cited by 74 · see citing works
Frangioni, B., Arnoux, P., Sabaty, M., Pignol, D., Bertrand, P., Guigliarelli, B., & Léger, C. (2004) · Journal of the American Chemical Society · doi:10.1021/ja0384072 · Cited by 70 · see citing works
The Electronic Structure and Spectroscopy of Metallo‐Dithiolene Complexes
Kirk, M. L., McNaughton, R. L., & Helton, M. E. (2003) · Progress in inorganic chemistry · doi:10.1002/0471471933.ch3 · Cited by 66 · see citing works
Brondino, C. D., Rivas, M. G., Romão, M. J., Moura, J. J. G., & Moura, I. (2006) · Accounts of Chemical Research · doi:10.1021/ar050104k · Cited by 49 · see citing works
González, P. J., Rivas, M. G., Brondino, C. D., Bursakov, S. A., Moura, I., & Moura, J. J. G. (2006) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-006-0110-0 · Cited by 45 · see citing works
Joshi, H., & Enemark, J. H. (2004) · Journal of the American Chemical Society · doi:10.1021/ja046465x · Cited by 35 · see citing works
Hofmann, M. (2007) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-007-0271-5 · Cited by 29 · see citing works
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Quantum Chemical Studies of Mechanisms for Metalloenzymes
Blomberg, M. R. A., Borowski, T., Himo, F., Liao, R., & Siegbahn, P. E. M. (2014) · Chemical Reviews · doi:10.1021/cr400388t · Cited by 602 · see citing works
Nitrate and periplasmic nitrate reductases
Sparacino-Watkins, C., Stolz, J. F., & Basu, P. (2014) · Chem. Soc. Rev. · doi:10.1039/c3cs60249d · Cited by 426 · see citing works
Biological chemistry of hydrogen sulfide and persulfides
Cuevasanta, E., Möller, M. N., & Álvarez, B. (2016) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2016.09.018 · Cited by 202 · see citing works
The prokaryotic Mo/W-bisPGD enzymes family: A catalytic workhorse in bioenergetic
Grimaldi, S., Schoepp‐Cothenet, B., Ceccaldi, P., Guigliarelli, B., & Magalon, A. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.01.011 · Cited by 159 · see citing works
Enzyme Mimetic Active Intermediates for Nitrate Reduction in Neutral Aqueous Media
Li, Y., Go, Y. K., Ooka, H., He, D., Jin, F., Kim, S. H., & Nakamura, R. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202002647 · Cited by 140 · see citing works
Millikin, R. J., Bianco, C. L., White, C. J., Saund, S. S., Henriquez, S., Alfaro, V. S., Akaike, T., Kumagai, Y., Soeda, S., Toscano, J. P., et al. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.05.013 · Cited by 106 · see citing works
Structural and mechanistic insights on nitrate reductases
Coelho, C., & Romão, M. J. (2015) · Protein Science · doi:10.1002/pro.2801 · Cited by 96 · see citing works
Coelho, C., González, P. J., Moura, J. G., Moura, I., Trincão, J., & João Romão, M. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.03.016 · Cited by 97 · see citing works
Molybdenum as an Essential Element for Crops: An Overview
Hu, C. (2020) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2020.24.004104 · Cited by 82 · see citing works
Cerqueira, N. M. F. S. A., Fernandes, P. A., González, P. J., Moura, J. J. G., & Ramos, M. J. (2013) · Inorganic Chemistry · doi:10.1021/ic3028034 · Cited by 62 · see citing works
Theoretical studies on the reactivity of molybdenum enzymes
Metz, S., & Thiel, W. (2011) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2011.01.027 · Cited by 54 · see citing works
González, P. J., Rivas, M. G., Mota, C., Brondino, C. D., Moura, I., & Moura, J. J. G. (2012) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2012.05.020 · Cited by 44 · see citing works
Biaso, F., Burlat, B., & Guigliarelli, B. (2012) · Inorganic Chemistry · doi:10.1021/ic201533p · Cited by 40 · see citing works
Cerqueira, N. M. F. S. A., González, P. J., Fernandes, P. A., Moura, J. J. G., & Ramos, M. J. (2015) · Accounts of Chemical Research · doi:10.1021/acs.accounts.5b00333 · Cited by 40 · see citing works
Jacques, J. G. J., Fourmond, V., Arnoux, P., Sabaty, M., Étienne, É., Grosse, S., Biaso, F., Bertrand, P., Pignol, D., Léger, C., et al. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.10.013 · Cited by 35 · see citing works
Reassessing the Strategies for Trapping Catalytic Intermediates during Nitrate Reductase Turnover
Fourmond, V., Sabaty, M., Arnoux, P., Bertrand, P., Pignol, D., & Léger, C. (2010) · The Journal of Physical Chemistry B · doi:10.1021/jp911443y · Cited by 33 · see citing works
Fukuto, J. M., Vega, V. S., Works, C., & Lin, J. (2020) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.11.013 · Cited by 34 · see citing works
Liao, R., Yu, J., & Himo, F. (2011) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2011.03.020 · Cited by 29 · see citing works
Theoretical studies on mechanisms of some Mo enzymes
Cerqueira, N. M. F. S. A., Pakhira, B., & Sarkar, S. (2015) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-015-1237-7 · Cited by 26 · see citing works
Fukuto, J. M. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0096 · Cited by 21 · see citing works
Enzymatic Reduction of Nitrate to Nitrite: Insight from Density Functional Calculations
Xie, H., & Cao, Z. (2009) · Organometallics · doi:10.1021/om9008197 · Cited by 20 · see citing works
Structure, Function, and Mechanism of Pyranopterin Molybdenum and Tungsten Enzymes
Ingersol, L. J., & Kirk, M. L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.14929-7 · Cited by 16 · see citing works
Enzyme Mimetic Active Intermediates for Nitrate Reduction in Neutral Aqueous Media
Li, Y., Go, Y. K., Ooka, H., He, D., Jin, F., Kim, S. H., & Nakamura, R. (2020) · Angewandte Chemie · doi:10.1002/ange.202002647 · Cited by 15 · see citing works
Silaghi-Dumitrescu, R. L., Mich, M., Matyas, C., & Cooper, C. E. (2011) · Nitric Oxide · doi:10.1016/j.niox.2011.11.004 · Cited by 15 · see citing works
Enzymatic “tricks”: Carboxylate shift and sulfur shift
Sousa, S. F., Cerqueira, N. M. F. S. A., Brás, N. F., Fernandes, P. A., & Ramos, M. J. (2014) · International Journal of Quantum Chemistry · doi:10.1002/qua.24689 · Cited by 14 · see citing works
Virtual Reality as a Medium of Asynchronous Content Delivery for Teaching about Enzymes
Abbasi, I., Rasool, S., & Habib, U. (2023) · Journal of Chemical Education · doi:10.1021/acs.jchemed.2c01113 · Cited by 10 · see citing works
Microbial Denitrification: Active Site and Reaction Path Models Predict New Isotopic Fingerprints
Boettger, J. D., Neubauer, C., Kopf, S., & Kubicki, J. D. (2022) · ACS Earth and Space Chemistry · doi:10.1021/acsearthspacechem.2c00102 · Cited by 5 · see citing works
Xie, H., Lei, Q., & Fang, W. (2012) · Science China Chemistry · doi:10.1007/s11426-012-4729-0 · Cited by 5 · see citing works
Pterin-Containing Microbial Molybdenum Enzymes
Metzger, M. C., & Basu, P. (2022) · Advances in environmental microbiology · doi:10.1007/978-3-030-97185-4_13 · Cited by 5 · see citing works
Mononuclear Molybdenum-Containing Enzymes
Maia, L. B., & Moura, J. J. G. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.13932-0 · Cited by 4 · see citing works
Molybdenum- and Tungsten-Mediated Oxidations
Schulzke, C. (2013) · Elsevier eBooks · doi:10.1016/b978-0-08-097774-4.00926-8 · Cited by 3 · see citing works
Structure and function of periplasmic nitrate reductase
Mongkonpruthangkoon, C., Giri, N. C., & Basu, P. (2026) · Biochemical Society Transactions · doi:10.1042/bst20250033 · Cited by 2 · see citing works
Jacques, J. G. J. (2014) · theses.fr (ABES) · doi:10.70675/19852afbz7969z49e5z86b0z4baa30aa72b7
Molybdenum Nanoparticles for Stress Resilience
Imran, A., Iftikhar, H., Sharif, M. N., Khan, Z., Latef, A. A. H. A., Khan, H., & Hussain, Z. (2026) · Springer eBooks · doi:10.1007/978-3-032-24219-8_15
- Authors
- Hofmann, M.
- Affiliations
- Heidelberg University (DE)
- Corresponding author
- Hofmann, Matthias
- ORCID
- Hofmann, Matthias
- Venue
- JBIC Journal of Biological Inorganic Chemistry
- Published
- 2009-05-30
- Volume
- 14
- Issue
- 7
- Pages
- 1023-1035
- ISSN
- 0949-8257 (ISSN-L)
- 1432-1327
- OpenAlex
- W2024615956
- Cited by
- 35
- References
- 33
- Citations by year
- 2026: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 5 · 2018: 2 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 3
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- JBIC Journal of Biological Inorganic Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Physical Sciences › Chemistry › Organic Chemistry › Organometallic Complex Synthesis and Catalysis
- Keywords
- nitrate reductase, napA, Desulfovibrio desulfuricans, molybdenum active site, dithiolato ligands, hexacoordinate complexes
- MeSH terms
- Ligands, Models, Molecular, Molybdenum, Nitrates, Oxidation-Reduction, Computational Biology, Catalytic Domain, Periplasmic Proteins, Desulfovibrio desulfuricans, Nitrate Reductase, Biocatalysis
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