Steven Rokita

About

Steven Rokita is a professor of Chemistry at Johns Hopkins University and the director of the Chemistry-Biology Interface Graduate Training Program. He holds a B.S. in Chemistry from the University of California at Berkeley and a Ph.D. in Biological Chemistry from MIT under the direction of Christopher Walsh. His research program is centered on describing the structure and activity of biological macromolecules through their essential chemical reactivity, applying methods of organic synthesis, physical organic chemistry, protein and nucleic acid chemistry, biochemistry, and molecular biology to investigate enzyme catalysis and nucleic acid modification. His current projects include enzymatic dehalogenation and reversible covalent chemistry expressed by quinone methide intermediates. His work on reductive dehalogenation explores the biological and environmental roles of organohalides, focusing on enzymes like iodotyrosine deiodinase, which is crucial for human health and is found across various organisms. Additionally, his research on quinone methides involves designing sequence-specific alkylation strategies for DNA, with implications for DNA damage and repair mechanisms. Rokita's contributions advance understanding of flavin chemistry, enzyme mechanisms, and potential applications in bioremediation and molecular biology.

Research topics

• Combinatorial chemistry
• Organic chemistry
• Chemistry
• Stereochemistry
• Biochemistry
• Biology
• Photochemistry
• Genetics
• Computational biology

Selected publications

• Redox control of iodotyrosine deiodinase

  Protein Science · 2018-07-27 · 17 citations

  articleOpen accessSenior authorCorresponding

  Abstract The redox chemistry of flavoproteins is often gated by substrate and iodotyrosine deiodinase (IYD) has the additional ability to switch between reaction modes based on the substrate. Association of fluorotyrosine (F‐Tyr), an inert substrate analog, stabilizes single electron transfer reactions of IYD that are not observed in the absence of this ligand. The co‐crystal of F‐Tyr and a T239A variant of human IYD have now been characterized to provide a structural basis for control of its fl…

  PublisherOA PDFDOI

• The minimal structure for iodotyrosine deiodinase function is defined by an outlier protein from the thermophilic bacterium Thermotoga neapolitana

  Journal of Biological Chemistry · 2021 · 10 citations

  Senior authorCorresponding

  The nitroreductase superfamily of enzymes encompasses many flavin mononucleotide (FMN)-dependent catalysts promoting a wide range of reactions. All share a common core consisting of an FMN-binding domain, and individual subgroups additionally contain one to three sequence extensions radiating from defined positions within this core to support their unique catalytic properties. To identify the minimum structure required for activity in the iodotyrosine deiodinase subgroup of this superfamily, att…

  PublisherDOI

• Toward a Halophenol Dehalogenase from Iodotyrosine Deiodinase via Computational Design

  ACS Catalysis · 2018-11-07 · 10 citations

  articleSenior authorCorresponding

  Reductive dehalogenation offers an attractive approach for removing halogenated pollutants from the environment, and iodotyrosine deiodinase (IYD) may contribute to this process after it can be engineered to accept a broad range of substrates. The selectivity of IYD is controlled in part by an active site loop of ∼26 amino acids. In the absence of a substrate, the loop is disordered and only folds into a compact helix-turn-helix upon halotyrosine association. The design algorithm of Rosetta was…

  PublisherDOI

• ¹⁹F NMR Reveals the Dynamics of Substrate Binding and Lid Closure for Iodotyrosine Deiodinase as a Complement to Steady-State Kinetics and Crystallography

  Biochemistry · 2024-08-13 · 9 citations

  articleOpen accessSenior authorCorresponding

  Active site lids are common features of enzymes and typically undergo conformational changes upon substrate binding to promote catalysis. Iodotyrosine deiodinase is no exception and contains a lid segment in all of its homologues from human to bacteria. The solution-state dynamics of the lid have now been characterized using 19F NMR spectroscopy with a CF3-labeled enzyme and CF3O-labeled ligands. From two-dimensional 19F–19F NMR exchange spectroscopy, interconversion rates between the free and b…

  PublisherOA PDFDOI

• Sequence Conservation Does Not Always Signify a Functional Imperative as Observed in the Nitroreductase Superfamily

  Biochemistry · 2022-03-23 · 8 citations

  articleOpen accessSenior authorCorresponding

  Consensus sequences have the potential to help classify the structure and function of proteins and highlight key regions that may contribute to their biological properties. Often, the level of significance will track with the extent of sequence conservation, but this should not be considered universal. Arg and Lys dominate a position adjacent to the N1 and C2 carbonyl of flavin mononucleotide (FMN) bound in the proteins of the nitroreductase superfamily. Although this placement satisfies expecta…

  PublisherOA PDFDOI

Recent grants

• The Reversibility of DNA Alkylation by a Quinone Methide

  NSF · $382k · 2005–2009

• NIH Grant R01CA043593

  NIH · $235k · 1990

• NIH Grant R01GM047531

  NIH · $1.5M · 2004

Frequent coauthors

• Cynthia J. Burrows

  University of Utah

  77 shared

• Kenneth D. Karlin

  Johns Hopkins University

  65 shared

• Lei Li

  University of Maryland, College Park

  36 shared

• James G. Muller

  33 shared

• Arnold L. Rheingold

  University of California, San Diego

  31 shared

• Glenn P. A. Yap

  Indiana University Bloomington

  31 shared

• Joshua Telser

  Roosevelt University

  28 shared

• Narasimha N. Murthy

  26 shared

Labs

• Rokita LaboratoryPI

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