Our laboratory is interested in three main areas: DNA topoisomerases, catalytic RNA molecules, and the molecular basis of spectrin flexibility.
DNA topoisomerases. The long term goal of our
work is to understand the catalytic mechanism of these molecules
in atomic detail. In particular, we are interested in understanding
how these enzymes perform complex topological rearrangements of DNA
molecules. DNA topoisomerases are of interest for several reasons:
1) they are responsible for maintaining the topological state of
DNA and are involved in a variety of crucial cellular processes.
2) Their involvement in key processes has lead to the development
of drugs whose target is topoisomerases. 3) Topoisomerases catalyze
a complex reaction that involves cutting and resealing the DNA and
passing DNA strands through this break. These reactions are not easy
to visualize or understand. The structures of several topoisomerases
and fragments of them have truly led to a near-atomic picture of
the way a very complex reaction is catalyzed. 4) Topoisomerases are
excellent examples of complex molecular machines that perform a complicated
reaction in the cell. Type I enzymes work in the absence of an external
energy source, such as ATP, and for this reason present an opportunity
to understand a process where the energy to drive large domain movements
is harnessed from the energy stored in the DNA, and 5) The structural
studies may provide the information to develop new chemotherapeutic
We are now also focusing our attention on repeats of human spectrin that contain the region involved in interactions with other cytoskeletal proteins such as ankyrin. We are employing a combination of biophysical and structural approaches with the long term goal of understanding the atomic basis of the interaction of spectrin and other cellular proteins.
Bacterial topoisomerase I and topoisomerase III relax supercoiled DNA via distinct pathways. Terekhova K, Gunn KH, Marko JF, and Mondragón A. Nucleic Acids Research. 2012 November;40(20):10432-10440.
The bacterial ribonuclease P holoenzyme requires specific, conserved residues for efficient catalysis and substrate positioning. Reiter NJ, Osterman AK, and Mondragón A. Nucleic Acids Research. 2012 November;40(20):10384-10393.
Structurally Similar but Functionally Diverse ZU5 Domains in Human Erythrocyte Ankyrin. Yasunaga M, Ipsaro JJ, and Mondragón A. Journal of Molecular Biology. 2012 April 6;417(4):336-350.
Emerging structural themes in large RNA molecules. Reiter NJ, Chan CW, and Mondragón A. Current Opinion in Structural Biology. 2011 June;21(3):319-326.
Preference by Exclusion. Godley LA and Mondragón A. Science. 2011 February 25;331(6020):1017-1018.
Solution structures of DNA-bound gyrase. Baker NM, Weigand S, Maar-Mathias S, and Mondragón A. Nucleic Acids Research. 2011 January;39(2):755-766.
Structure of a bacterial ribonuclease P holoenzyme in complex with tRNA. Reiter NJ, Osterman A, Torres-Larios A, Swinger KK, Pan T, and Mondragón A. Nature. 2010 December 9;468(7325):784-789.
Structures of Minimal Catalytic Fragments of Topoisomerase V Reveals Conformational Changes Relevant for DNA Binding. Rajan R, Taneja B, and Mondragón A. Structure. 2010 July 14;18(7):829-838.
Crystal structure and functional interpretation of the erythrocyte spectrin tetramerization domain complex. Ipsaro JJ, Harper SL, Messick TE, Marmorstein R, Mondragón A, and Speicher DW. Blood. 2010 June 10;115(23):4843-4852.
Crystal Structure of a Bacterial Topoisomerase IB in Complex with DNA Reveals a Secondary DNA Binding Site. Patel A, Yakovleva L, Shuman S, and Mondragón A. Structure. 2010 June 9;18(6):725-733.
View all publications by Alfonso Mondragón listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.