Honors & Awards


  • CMAD Fellowship, The Center for Molecular Analysis and Design, Stanford University (2016 July)

Education & Certifications


  • B.Sc, University of Michigan, Biochemistry (2014)

2015-16 Courses


All Publications


  • Mg2+ Shifts Ligand-Mediated Folding of a Riboswitch from Induced-Fit to Conformational Selection JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Suddala, K. C., Wang, J., Hou, Q., Water, N. G. 2015; 137 (44): 14075-14083

    Abstract

    Bacterial riboswitches couple small-molecule ligand binding to RNA conformational changes that widely regulate gene expression, rendering them potential targets for antibiotic intervention. Despite structural insights, the ligand-mediated folding mechanisms of riboswitches are still poorly understood. Using single-molecule fluorescence resonance energy transfer (smFRET), we have investigated the folding mechanism of an H-type pseudoknotted preQ1 riboswitch in dependence of Mg(2+) and three ligands of distinct affinities. We show that, in the absence of Mg(2+), both weakly and strongly bound ligands promote pseudoknot docking through an induced-fit mechanism. By contrast, addition of as low as 10 μM Mg(2+) generally shifts docking toward conformational selection by stabilizing a folded-like conformation prior to ligand binding. Supporting evidence from transition-state analysis further highlights the particular importance of stacking interactions during induced-fit and of specific hydrogen bonds during conformational selection. Our mechanistic dissection provides unprecedented insights into the intricate synergy between ligand- and Mg(2+)-mediated RNA folding.

    View details for DOI 10.1021/jacs.5b09740

    View details for Web of Science ID 000364727600019

    View details for PubMedID 26471732

  • Meeting Report: SMART Timing-Principles of Single Molecule Techniques Course at the University of Michigan 2014 BIOPOLYMERS Bartke, R. M., Cameron, E. L., Cristie-David, A. S., Custer, T. C., Denies, M. S., Daher, M., Dhakal, S., Ghosh, S., Heinicke, L. A., Hoff, J. D., Hou, Q., Kahlscheuer, M. L., Karslake, J., Krieger, A. G., Li, J., Li, X., Lund, P. E., Vo, N. N., Park, J., Pitchiaya, S., Rai, V., Smith, D. J., Suddala, K. C., Wang, J., Widom, J. R., Walter, N. G. 2015; 103 (5): 296-302

    Abstract

    Four days after the announcement of the 2014 Nobel Prize in Chemistry for "the development of super-resolved fluorescence microscopy" based on single molecule detection, the Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan hosted a "Principles of Single Molecule Techniques 2014" course. Through a combination of plenary lectures and an Open House at the SMART Center, the course took a snapshot of a technology with an especially broad and rapidly expanding range of applications in the biomedical and materials sciences. Highlighting the continued rapid emergence of technical and scientific advances, the course underscored just how brightly the future of the single molecule field shines.

    View details for DOI 10.1002/bip.22603

    View details for Web of Science ID 000350306700005

    View details for PubMedID 25546606

  • Recent Advances in Radical SAM Enzymology: New Structures and Mechanisms ACS CHEMICAL BIOLOGY Wang, J., Woldring, R. P., Roman-Melendez, G. D., McClain, A. M., Alzua, B. R., Marsh, E. N. 2014; 9 (9): 1929-1938

    Abstract

    The radical S-adenosylmethionine (SAM) superfamily of enzymes catalyzes an amazingly diverse variety of reactions ranging from simple hydrogen abstraction to complicated multistep rearrangements and insertions. The reactions they catalyze are important for a broad range of biological functions, including cofactor and natural product biosynthesis, DNA repair, and tRNA modification. Generally conserved features of the radical SAM superfamily include a CX3CX2C motif that binds an [Fe4S4] cluster essential for the reductive cleavage of SAM. Here, we review recent advances in our understanding of the structure and mechanisms of these enzymes that, in some cases, have overturned widely accepted mechanisms.

    View details for DOI 10.1021/cb5004674

    View details for Web of Science ID 000342121200003

    View details for PubMedID 25009947