Edwin Antony

Edwin Antony

Assistant Professor
Wehr Life Sciences, 209
(414) 288-1474
E-mail

Lab Website

Ph.D. Wesleyan University
Post-doctoral Fellow, Johns Hopkins University
Post-doctoral Fellow, Washington University School of Medicine

 

Our research aims at understanding how ATP utilizing enzymes function. In particular, we explore how the energy from ATP binding and hydrolysis is utilized to achieve biological function.  Adenosine triphosphate (ATP) is the fuel source for the activity of several enzymes. We work on three classes of ATPases: 1. Helicases/translocases that work on nucleic acids (DNA/RNA), 2. Oxidoreductase ATPases and 3. Fe-S cluster containing helicases. We use a combination of pre-steady state enzymatic and structural approaches to build quantitative models of enzyme activity in order to understand how they function in the cell.

Antony Helicases
1. Helicases
     Helicases are enzymes that unwind double stranded DNA. They also move along a ssDNA lattice and remove other proteins bound on DNA. For both activities they use the energy from ATP binding and hydrolysis to move along DNA. One such helicase/translocase is the Srs2 protein that functions as an anti-recombinase in homologous recombination (HR). Srs2 removes the Rad51 filament from ssDNA thereby blocking HR. We are investigating how Srs2 functions in HR and how it utilizes ATP. Mediator proteins affect the activity of Srs2 and the Rad51 filament. The dynamic interplay between mediator proteins, Rad51 and Srs2 is held in fine balance in the cell. Our second line of investigation seeks to understand the mechanisms underpinning these interactions. 

Antony Oxidoructases
2. Oxidoreductases
     In collaboration with the Seefeldt group we are interested in understanding how oxidoreductases use ATP to mediate substrate reduction. We are investigating the coupling between electron transfer and ATP hydrolysis in nitrogease and DPOR enzyme complexes. Nitrogenase catalyzes the reduction of dinitrogen to ammonia and uses 16 ATP molecules per substrate reduced. The dark operative protochlorophyllide reductase (DPOR) complex similarly reduces Pchlide to Chlide and substrate reduction is coupled to ATP hydrolysis. Both these multiprotein assemblies orchestrate step-wise molecular events to enact substrate reduction. These steps are associated with large conformational changes in the protein complex. Our long-term goal is to understand how ATP is utilized to orchestrate substrate reduction.

Antony Fe-S Helicases
3. Fe-S Helicases
     A second class of helicases we are investigating possess an unique combination of Fe-S metalloclusters and ATPase activity. The FancJ and RTEL1 helicases are two examples of such metalloproteins and play a role in maintaining genomic integrity. We are addressing three specific questions: a) what is the precise role of the Fe-S cluster in these helicases? b) How is the Fe-S cluster inserted into these helicases during biogenesis? c) How do these helicases use ATP to function during DNA unwinding and translocation?

 

 

 

Selected Publications

Negative cooperativity in the nitrogenase Fe protein electron delivery cycle.

Danyal K, Shaw S, Page TR, Duval S, Horitani M, Marts AR, Lukoyanov D, Dean DR, Raugei S, Hoffman BM, Seefeldt LC, Antony E. Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):E5783-E5791.

 

Rad51 Nucleoprotein Filament Disassembly Captured Using Fluorescent Plasmodium falciparum SSB as a Reporter for Single-Stranded DNA.

Davenport EP, Harris DF, Origanti S, Antony E. PLoS One. 2016 Jul 14;11(7):e0159242. 

 

Spa47 is an oligomerization-activated type three secretion system (T3SS) ATPase from Shigella flexneri.

Burgess JL, Jones HB, Kumar P, Toth RT 4th, Middaugh CR, Antony E, Dickenson NE. Protein Sci. 2016 May;25(5):1037-48. doi: 10.1002/pro.2917. Epub 2016 Mar 22.

 

Evidence That the Pi Release Event Is the Rate-Limiting Step in the Nitrogenase Catalytic Cycle.

Yang ZY, Ledbetter R, Shaw S, Pence N, Tokmina-Lukaszewska M, Eilers B, Guo Q, Pokhrel N, Cash VL, Dean DR, Antony E, Bothner B, Peters JW, Seefeldt LC. Biochemistry. 2016 Jul 5;55(26):3625-35.

 

Context-dependent remodeling of Rad51-DNA complexes by Srs2 is mediated by a specific protein-protein interaction.

Lytle AK, Origanti SS, Qiu Y, VonGermeten J, Myong S, Antony E. J Mol Biol. 2014 May 1;426(9):1883-97. 

 

Establishing the order of electron transfer and ATP hydrolysis in Nitrogenase.

Duval S., Danyal K., Shaw S., Dean D.R., Hoffman B.M., Antony E and Seefeldt L.C. Proc Natl Acad Sci U S A. 2013. 110:16414-16419 

 

Intrinsically disordered C-terminal tails of E. coli single-stranded DNA binding protein regulate cooperative binding to single-stranded DNA.

Kozlov AG, Weiland E, Mittal A, Waldman V, Antony E, Fazio N, Pappu RV, Lohman TM. J Mol Biol. 2015 Feb 27;427(4):763-74

 

 

 

Current Students

Elliot Corless (Ph.D. student)

Nilisha Pokhrel (Ph.D. student)

Dr. Antony is currently accepting new Ph.D. students into his lab

 



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Biological Sciences Department

Marquette University, Wehr Life Sciences
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P.O. Box 1881
Milwaukee, WI 53201-1881
(414) 288-7355