Publication Date:
2014-09-27
Description:
The mechanism of nitrogenase remains enigmatic, with a major unresolved issue concerning how inhibitors and substrates bind to the active site. We report a crystal structure of carbon monoxide (CO)-inhibited nitrogenase molybdenum-iron (MoFe)-protein at 1.50 angstrom resolution, which reveals a CO molecule bridging Fe2 and Fe6 of the FeMo-cofactor. The mu2 binding geometry is achieved by replacing a belt-sulfur atom (S2B) and highlights the generation of a reactive iron species uncovered by the displacement of sulfur. The CO inhibition is fully reversible as established by regain of enzyme activity and reappearance of S2B in the 1.43 angstrom resolution structure of the reactivated enzyme. The substantial and reversible reorganization of the FeMo-cofactor accompanying CO binding was unanticipated and provides insights into a catalytically competent state of nitrogenase.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205161/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205161/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spatzal, Thomas -- Perez, Kathryn A -- Einsle, Oliver -- Howard, James B -- Rees, Douglas C -- GM45162/GM/NIGMS NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- R01 GM045162/GM/NIGMS NIH HHS/ -- R37 GM045162/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Sep 26;345(6204):1620-3. doi: 10.1126/science.1256679.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Division of Chemistry and Chemical Engineering, MailCode 114-96, California Institute of Technology, Pasadena, CA 91125, USA. spatzal@caltech.edu dcrees@caltech.edu. ; Howard Hughes Medical Institute and Division of Chemistry and Chemical Engineering, MailCode 114-96, California Institute of Technology, Pasadena, CA 91125, USA. ; Institut fur Biochemie, Albert-Ludwigs-Universitat Freiburg, 79104 Freiburg, Germany. BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universitat Freiburg, 79104 Freiburg, Germany. ; Howard Hughes Medical Institute and Division of Chemistry and Chemical Engineering, MailCode 114-96, California Institute of Technology, Pasadena, CA 91125, USA. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25258081" target="_blank"〉PubMed〈/a〉
Keywords:
Carbon Monoxide/*chemistry
;
Catalytic Domain
;
Crystallography, X-Ray
;
Enzyme Activation
;
Ligands
;
Molybdoferredoxin/antagonists & inhibitors/*chemistry
;
*Nitrogen Fixation
;
Protein Binding
;
Sulfur/chemistry
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
