10. Iron-sulfur clusters and molecular oxygen: function, adaptation, degradation, and repair

Author(s):  
Yvain Nicolet ◽  
Juan C. Fontecilla-Camps
2014 ◽  
Vol 47 (10) ◽  
pp. 3196-3205 ◽  
Author(s):  
Jason C. Crack ◽  
Jeffrey Green ◽  
Andrew J. Thomson ◽  
Nick E. Le Brun

Science ◽  
2021 ◽  
pp. eabi5224
Author(s):  
Nunziata Maio ◽  
Bernard A. P. Lafont ◽  
Debangsu Sil ◽  
Yan Li ◽  
J. Martin Bollinger ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes. We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron microscopy structures of the RdRp complex. These metal binding sites are essential for replication and for interaction with the viral helicase. Oxidation of the clusters by the stable nitroxide TEMPOL caused their disassembly, potently inhibited the RdRp, and blocked SARS-CoV-2 replication in cell culture. These iron-sulfur clusters thus serve as cofactors for the SARS-CoV-2 RdRp and are targets for therapy of COVID-19.


Author(s):  
Han Sol Jeong ◽  
Sugyeong Hong ◽  
Hee Seon Yoo ◽  
Jin Kim ◽  
Yujeong Kim ◽  
...  

Methane monooxygenase (MMO) has attracted significant attention owing to its crucial role in the global carbon cycle; it impedes greenhouse effects by converting methane to methanol under ambient conditions. The...


2019 ◽  
Vol 7 (12) ◽  
pp. 671 ◽  
Author(s):  
Xin Nie ◽  
Bernhard Remes ◽  
Gabriele Klug

A multitude of biological functions relies on iron-sulfur clusters. The formation of photosynthetic complexes goes along with an additional demand for iron-sulfur clusters for bacteriochlorophyll synthesis and photosynthetic electron transport. However, photooxidative stress leads to the destruction of iron-sulfur clusters, and the released iron promotes the formation of further reactive oxygen species. A balanced regulation of iron-sulfur cluster synthesis is required to guarantee the supply of this cofactor, on the one hand, but also to limit stress, on the other hand. The phototrophic alpha-proteobacterium Rhodobacter sphaeroides harbors a large operon for iron-sulfur cluster assembly comprising the iscRS and suf genes. IscR (iron-sulfur cluster regulator) is an iron-dependent regulator of isc-suf genes and other genes with a role in iron metabolism. We applied reporter gene fusions to identify promoters of the isc-suf operon and studied their activity alone or in combination under different conditions. Gel-retardation assays showed the binding of regulatory proteins to individual promoters. Our results demonstrated that several promoters in a sense and antisense direction influenced isc-suf expression and the binding of the IscR, Irr, and OxyR regulatory proteins to individual promoters. These findings demonstrated a complex regulatory network of several promoters and regulatory proteins that helped to adjust iron-sulfur cluster assembly to changing conditions in Rhodobacter sphaeroides.


1998 ◽  
Vol 273 (21) ◽  
pp. 13264-13272 ◽  
Author(s):  
Limin Zheng ◽  
Valerie L. Cash ◽  
Dennis H. Flint ◽  
Dennis R. Dean

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