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Classifying the metal dependence of uncharacterized nitrogenases

McGlynn, Shawn E. and Boyd, Eric S. and Peters, John W. and Orphan, Victoria J. (2013) Classifying the metal dependence of uncharacterized nitrogenases. Frontiers in Microbiology, 3 . Art. No. 419. ISSN 1664-302X. PMCID PMC3578447.

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Nitrogenase enzymes have evolved complex iron–sulfur (Fe–S) containing cofactors that most commonly contain molybdenum (MoFe, Nif) as a heterometal but also exist as vanadium (VFe, Vnf) and heterometal-independent (Fe-only, Anf) forms. All three varieties are capable of the reduction of dinitrogen (N_2) to ammonia (NH_3) but exhibit differences in catalytic rates and substrate specificity unique to metal type. Recently, N_2 reduction activity was observed in archaeal methanotrophs and methanogens that encode for nitrogenase homologs which do not cluster phylogenetically with previously characterized nitrogenases. To gain insight into the metal cofactors of these uncharacterized nitrogenase homologs, predicted three-dimensional structures of the nitrogenase active site metal-cofactor binding subunits NifD, VnfD, and AnfD were generated and compared. Dendrograms based on structural similarity indicate nitrogenase homologs cluster based on heterometal content and that uncharacterized nitrogenase D homologs cluster with NifD, providing evidence that the structure of the enzyme has evolved in response to metal utilization. Characterization of the structural environment of the nitrogenase active site revealed amino acid variations that are unique to each class of nitrogenase as defined by heterometal cofactor content; uncharacterized nitrogenases contain amino acids near the active site most similar to NifD. Together, these results suggest that uncharacterized nitrogenase homologs present in numerous anaerobic methanogens, archaeal methanotrophs, and firmicutes bind FeMo-co in their active site, and add to growing evidence that diversification of metal utilization likely occurred in an anoxic habitat.

Item Type:Article
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URLURL TypeDescription DOIArticle CentralArticle
McGlynn, Shawn E.0000-0002-8199-7011
Orphan, Victoria J.0000-0002-5374-6178
Additional Information:© 2013 McGlynn, Boyd, Peters and Orphan. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. Received: 09 October 2012; Paper pending published: 02 November 2012; Accepted: 20 November 2012; Published online: 30 January 2013. Shawn E. McGlynn is an Agouron Geobiology Option postdoctoral fellow in the Division of Geological and Planetary Sciences at Caltech and is grateful for support provided by the Agouron Institute. Additional support for this work was provided by the Department of Energy Grant DE-SC0004949 (to Victoria J Orphan) and the NASA Astrobiology Institute (NAI) NNA08C-N85A (to John W. Peters and Eric S. Boyd). Eric S. Boyd also wishes to acknowledge support from the National Science Foundation (EAR-1123689 and PIRE-0968421). The authors are grateful for comments from Aaron D. Goldman, Joshua A. Steele, Wolfgang Nitschke, and members of the laboratory of Victoria Orphan.
Funding AgencyGrant Number
Agouron InstituteUNSPECIFIED
Department of Energy (DOE)DE-SC0004949
Subject Keywords:nitrogenase, metalloenzyme, molecular similarity, sequence conservation, vanadium, iron, molybdenum
PubMed Central ID:PMC3578447
Record Number:CaltechAUTHORS:20130320-133744148
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Official Citation:McGlynn SE, Boyd ES, Peters JW and Orphan VJ (2013) Classifying the metal dependence of uncharacterized nitrogenases. Front. Microbio. 3:419. doi:10.3389/fmicb.2012.00419
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:37576
Deposited By: Tony Diaz
Deposited On:25 Mar 2013 23:06
Last Modified:03 Oct 2019 19:38

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