QM/MM Study of the Nitrogenase MoFe Protein Resting
State: Broken-Symmetry States, Protonation States, and QM Region Convergence
in the FeMoco Active Site
Posted on 2017-10-20 - 19:19
Nitrogenase is one
of the most fascinating enzymes in nature, being responsible for all
biological nitrogen reduction. Despite decades of research, it is
among the enzymes in bioinorganic chemistry whose mechanism is the
most poorly understood. The MoFe protein of nitrogenase contains an
iron–molybdenum–sulfur cluster, FeMoco, where N2 reduction takes place. The resting state of FeMoco has been
characterized by crystallography, multiple spectroscopic techniques,
and theory (broken-symmetry density functional theory), and all heavy
atoms are now characterized. The cofactor charge, however, has been
controversial, the electronic structure has proved enigmatic, and
little is known about the mechanism. While many computational studies
have been performed on FeMoco, few have taken the protein environment
properly into account. In this study, we put forward QM/MM models
of the MoFe protein from Azotobacter vinelandii, centered on FeMoco. By a detailed analysis of the FeMoco geometry
and comparison to the atomic resolution crystal structure, we conclude
that only the [MoFe7S9C]1– charge is a possible resting state charge. Further, we find that
of the three lowest energy broken-symmetry solutions of FeMoco, the
BS7-235 spin isomer (where 235 refers to Fe atoms that are “spin-down”)
is the only one that can be reconciled with experiment. This is revealed
by a comparison of the metal–metal distances in the experimental
crystal structure, a rare case of spin-coupling phenomena being visible
through the molecular structure. This could be interpreted as the
enzyme deliberately stabilizing a specific electronic state of the
cofactor, possibly for tuning specific reactivity on specific metal
atoms. Finally, we show that the alkoxide group on the Mo-bound homocitrate
must be protonated under resting state conditions, the presence of
which has implications regarding the nature of FeMoco redox states
as well as for potential substrate reduction mechanisms.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Benediktsson, Bardi; Bjornsson, Ragnar (2017). QM/MM Study of the Nitrogenase MoFe Protein Resting
State: Broken-Symmetry States, Protonation States, and QM Region Convergence
in the FeMoco Active Site. ACS Publications. Collection. https://doi.org/10.1021/acs.inorgchem.7b02158
or
Select your citation style and then place your mouse over the citation text to select it.