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.
DNase H Activity of Neisseria meningitidis Cas9. Zhang Y, Rajan R, Seifert HS, Mondragón A, and Sontheimer EJ. Molecular Cell. 2015 October 15;60(2):242-255.
Allosteric transcriptional regulation via changes in the overall topology of the core promoter. Philips SJ, Canalizo-Hernandez M, Yildirim I, Schatz GC, Mondragón A, and O'Halloran TV. Science. 2015 August 21;349(6250):877-881.
Structural insights into the assembly of the histone deacetylase-associated Sin3L/Rpd3L corepressor complex. Clark MD, Marcum R, Graveline R, Chan CW, Xie T, Chen Z, Ding Y, Zhang Y, Mondragón A, David G, and Radhakrishnan I. PNAS. 2015 July 14;112(28):E3669-E3678.
Structural and Mechanistic Basis of Zinc Regulation Across the E. coli Zur Regulon. Gilston BA, Wang S, Marcus MD, Canalizo-Hernández MA, Swindell EP, Xue Y, Mondragón A, and O'Halloran TV. PLoS Biology. 2014 November 4;12(11):e1001987.
Biochemical Characterization of the Topoisomerase Domain of Methanopyrus kandleri Topoisomerase V. Rajan R, Osterman AK, Gast AT, and Mondragón A. Journal of Biological Chemistry. 2014 October 17;289(42):28898-28909.
Single-molecule analysis uncovers the difference between the kinetics of DNA decatenation by bacterial topoisomerases I and III. Terekhova K, Marko JF, and Mondragón A. Nucleic Acids Research. 2014 October 13;42(18):11657-11667.
Structure and function of the T-loop structural motif in noncoding RNAs. Chan CW, Chetnani B, and Mondragón A. Wiley Interdisciplinary Reviews: RNA. 2013 September/October;4(5):507-522.
Structural biology: RNA exerts self-control. Chetnani B and Mondragón A. Nature. 2013 August 15;500(7462):279-280.
Structural Studies of RNase P. Mondragón A. Annual Review of Biophysics. 2013 May;42:537-557.
Studies of bacterial topoisomerases I and III at the single-molecule level. Terekhova K, Marko JF, and Mondragón A. Biochemical Society Transactions. 2013 April 1;41(2):571-575.
Identification of one of the apurinic/apyrimidinic lyase active sites of topoisomerase V by structural and functional studies. Rajan R, Prasad R, Taneja B, Wilson SH, and Mondragón A. Nucleic Acids Research. 2013 January 7;41(1):657-666.
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.
View all publications by Alfonso Mondragón listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.