Substrate channel in nitrogenase revealed by a molecular dynamics approach

Dayle Smith, Karamatullah Danyal, Simone Raugei, Lance C. Seefeldt

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Abstract

Mo-dependent nitrogenase catalyzes the biological reduction of N 2 to two NH3 molecules at FeMo-cofactor buried deep inside the MoFe protein. Access of substrates, such as N2, to the active site is likely restricted by the surrounding protein, requiring substrate channels that lead from the surface to the active site. Earlier studies on crystallographic structures of the MoFe protein have suggested three putative substrate channels. Here, we have utilized submicrosecond atomistic molecular dynamics simulations to allow the nitrogenase MoFe protein to explore its conformational space in an aqueous solution at physiological ionic strength, revealing a putative substrate channel. The viability of this observed channel was tested by examining the free energy of passage of N2 from the surface through the channel to FeMo-cofactor, resulting in the discovery of a very low energy barrier. These studies point to a viable substrate channel in nitrogenase that appears during thermal motions of the protein in an aqueous environment and that approaches a face of FeMo-cofactor earlier implicated in substrate binding.

Original languageEnglish
Pages (from-to)2278-2285
Number of pages8
JournalBiochemistry
Volume53
Issue number14
DOIs
Publication statusPublished - Apr 15 2014

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ASJC Scopus subject areas

  • Biochemistry

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