Area of Interest
Throughout evolution, iron-sulfur proteins have become an integral part of multiple physiological processes including energy metabolism, biosynthesis of heme, biotin, lipoid acid, thiamine, nicotinamides, molybdenum, ubiquinone, and a number of amino acids, gene translation, RNA modification, DNA replication and repair, and regulation of gene expression. The overall goal of our research is to understand iron-sulfur cluster biogenesis and specific functions of iron-sulfur clusters in proteins.
Iron homeostasis and iron-sulfur cluster biogenesis. Using Escherichia coli as a model organism, we have shown that a highly conserved protein IscA is able to recruit intercellular iron and deliver iron for iron-sulfur cluster assembly in proteins. Deletion of IscA and its paralog SufA in E. coli results in deficiency of iron-sulfur cluster biogenesis and a null-growth phenotype. Our current research aims to illustrate how cells may regulate intracellular iron homeostasis and iron-sulfur cluster biogenesis in response to oxidative stress and energy metabolism in cells.
Redox regulation of the mitochondrial outer membrane protein mitoNEET. Human mitoNEET is a primary target of type II drug pioglitazone. Misregulation of mitoNEET expression has also been associated with neurodegenerative diseases, cardiovascular diseases, and breast cancer development. MitoNEET is a homodimer with each monomer hosting a redox active [2Fe-2S] cluster via three cysteine and one histidine residues. The ongoing research aims to illustrate mechanism underlying redox regulation of energy metabolism in mitochondria by mitoNEET.
Wang, Y., Landry, A. P. & Ding, H. (2017) The mitochondrial outer membrane protein mitoNEET is a redox enzyme catalyzing electron transfer from FMNH2 to oxygen or ubiquinone. J. Biol. Chem. jbc.M117.789800 (Epub ahead of print).
Tan G, Yang J, Li T, Zhao J, Sun S, Li X, Lin C, Li J, Zhou H, Lyu J, & Ding H. (2017) Anaerobic copper toxicity and iron-sulfur cluster biogenesis in Escherichia coli. Appl Environ Microbiol. doi: 10.1128/AEM.00867-17. [Epub ahead of print] PMID: 28576762.
Cheng, Z., Landry, A. P., Wang, Y. & Ding, H. (2017) Binding of nitric oxide in the CDGSH-type [2Fe-2S] clusters of human mitochondrial protein Miner2. J. Biol. Chem. 292, 3146-3153.
Landry, A. P., Wang, Y., Cheng, Z., Crochet, R.B., Lee, Y.H., & Ding, H. (2017) Flavin nucleotides act as electron shuttles mediating reduction of the [2Fe-2S] clusters in mitochondrial outer membrane protein mitoNEET. Free Radic. Biol. Med. 102, 240-247.
Yang, J., Tan, G., Zhang, T., White, R. H., Lu, J., & Ding H. (2015) Deletion of the proposed iron chaperones IscA/SufA results in accumulation of a red intermediate cysteine desulfurase IscS in Escherichia coli. J. Biol. Chem. 290, 14226-14234.
Landry, A. P., Cheng, Z., & Ding, H. (2015) Reduction of mitochondrial protein mitoNEET [2Fe-2S] clusters by human glutathione reductase. Free Radic. Biol. Med. 81, 119-127.
Huang, C. Y, Abe, Y., Ding, H. & Chung, I.F. (2015) Helicase and its interacting factors: regulation mechanism, characterization, structure, and application for drug design. Biomed. Res. Int. 2015, 909047.
Landry, A. P., & Ding, H. (2014) Redox control of human mitochondrial outer membrane protein mitoNEET [2Fe-2S] clusters by biological thiols and hydrogen peroxide. J. Biol. Chem. 289, 4307-4315.
Tan, G., Cheng, Z., Peng, Y., Landry, A. P., Lu, J., & Ding, H. (2014) Copper binding in IscA inhibits iron-sulphur cluster assembly in Escherichia coli. Mol. Microbiol. 93,629-644.
Cheng, Z., Tan, G., Wang, W., Su, X., Landry. A. P., Lu, J., & Ding, H. (2014) Iron and zinc binding activity of Escherichia coli topoisomerase I homolog YrdD. Biometals, 27, 229-236.
Landry, A. P. & Ding, H. (2014) The N-terminal domain of human DNA helicase Rtel1 contains a redox active iron-sulfur cluster. Biomed Res Int. 2014:285791.
Landry, A. P., Cheng, Z., & Ding, H. (2013) Iron binding is essential for the function of IscA in iron-sulfur cluster biogenesis. Dalton Trans. 42, 3100-3106.
Cheng, Z., Caillet, A., Ren, B., & Ding, H. (2012) Stimulation of Escherichia coli DNA damage inducible DNA helicase DinG by the single-stranded DNA binding protein SSB. FEBS Lett. 586, 3825-3830.
Tan, G., Landry, A. P., Dai, R., Wang, L., Lu, J., & Ding, H. (2012) Competition of zinc ion for the [2Fe-2S] cluster binding site in the diabetes drug target protein mitoNEET. Biometals. 25, 1177-1184.
Landry, A. P., Duan, X., Huang, H., & Ding, H. (2011) Iron-sulfur proteins are the major source of protein-bound dinitrosyl iron complexes formed in Escherichia coli cells under nitric oxide stress. Free Radic. Biol. Med. 50, 1528-1590.