Nitrogenase reaction represents a major source of the usable form of nitrogen that supports the existence of human population. As such, understanding how small building blocks are assembled into a functional nitrogenase entity is of significant relevance to human health. Using combined genetic, biochemical, spectroscopic and structural approaches, we propose to investigate how M-cluster, the active center of molybdenum nitrogenase, is assembled. Specifically, we will examine the formation of a Fe-S core of M-cluster, the maturation of Fe-S core into an M-cluster, and the transfer of M-cluster from the assembly site to its target location in great detail. Through our proposed studies, we expect to refine the biosynthetic pathway of M-cluster, which will provide crucial insights into th structural-functional relationship of nitrogenase and the general assembly mechanism of complex metal clusters in biological systems.

Public Health Relevance

Using combined genetic, biochemical, spectroscopic and structural approaches, we propose to investigate how M-cluster, the active center of molybdenum nitrogenase, is assembled. Through our proposed studies, we expect to refine the biosynthetic mechanism of M-cluster, which will provide crucial insights into the structural-functional relationship of nitrogenase and the general assembly scheme of complex metal clusters in biological systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM067626-11
Application #
8598093
Study Section
Macromolecular Structure and Function A Study Section (MSFA)
Program Officer
Anderson, Vernon
Project Start
2003-05-01
Project End
2016-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
11
Fiscal Year
2014
Total Cost
$277,798
Indirect Cost
$93,298
Name
University of California Irvine
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Hu, Yilin; Ribbe, Markus W (2015) Nitrogenase and homologs. J Biol Inorg Chem 20:435-45
Lee, Chi Chung; Hu, Yilin; Ribbe, Markus W (2015) Catalytic reduction of CN-, CO, and CO2 by nitrogenase cofactors in lanthanide-driven reactions. Angew Chem Int Ed Engl 54:1219-22
Rebelein, Johannes G; Hu, Yilin; Ribbe, Markus W (2014) Differential reduction of CO? by molybdenum and vanadium nitrogenases. Angew Chem Int Ed Engl 53:11543-6
Hu, Yilin; Ribbe, Markus W (2014) A journey into the active center of nitrogenase. J Biol Inorg Chem 19:731-6
Ribbe, Markus W; Hu, Yilin; Hodgson, Keith O et al. (2014) Biosynthesis of nitrogenase metalloclusters. Chem Rev 114:4063-80
Rupnik, Kresimir; Lee, Chi Chung; Wiig, Jared A et al. (2014) Nonenzymatic synthesis of the P-cluster in the nitrogenase MoFe protein: evidence of the involvement of all-ferrous [Fe4S4](0) intermediates. Biochemistry 53:1108-16
Hu, Yilin; Ribbe, Markus W (2013) Biosynthesis of the iron-molybdenum cofactor of nitrogenase. J Biol Chem 288:13173-7
Lancaster, Kyle M; Hu, Yilin; Bergmann, Uwe et al. (2013) X-ray spectroscopic observation of an interstitial carbide in NifEN-bound FeMoco precursor. J Am Chem Soc 135:610-2
Wiig, Jared A; Lee, Chi Chung; Hu, Yilin et al. (2013) Tracing the interstitial carbide of the nitrogenase cofactor during substrate turnover. J Am Chem Soc 135:4982-3
Hu, Yilin; Ribbe, Markus W (2013) Nitrogenase assembly. Biochim Biophys Acta 1827:1112-22

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