skip to main content

Title: Substrate Channel in Nitrogenase Revealed by a Molecular Dynamics Approach

Mo-dependent nitrogenase catalyzes the biological reduction of N2 to 2NH3 at the 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 sub-microsecond 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 not previously reported. The viability of the proposed channel was tested by examining the free energy of passage of N2 from the surface through the channel to FeMo-cofactor, with 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 that approaches a face of FeMo-cofactor earlier implicated in substrate binding.
 [1] ;  [2] ;  [1] ;  [2]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  2. Utah State Univ., Logan, UT (United States)
Publication Date:
OSTI Identifier:
Report Number(s):
Journal ID: ISSN 0006-2960; 2388; 2387; KC0304020
DOE Contract Number:
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemistry; Journal Volume: 53; Journal Issue: 14
American Chemical Society (ACS)
Research Org:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org:
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES Environmental Molecular Sciences Laboratory