Daniel Herschlag

Honors and Awards

• Fellow, AAAS (2005)
• Merit Award, NIH (2002)
• Cope Scholar Award, ACS (2000)
• Established Investigator, AHA (1998-2002)
• Pfizer Award for Enzyme Chemistry, ACS (1997)
• Fellowship in Science and Engineering, David and Lucile Packard (1995-2000)
• Scholar, Searle (1993-1996)
• Scholar in Biomedical Science, Lucille P. Markey (1990-1997)
• Postdoctoral Fellowship, Helen Hay Whitney (Colorado; 1989-1990)
• Fellowship, Gillette Foundation (Brandeis; 1986-1987)
• Award for Excellence in Biochemistry, SUNY (1982)
• Award in Biochemistry, American Institute of Chemists (SUNY; 1982)
• Phi Beta Kappa, Michigan (1979)
• Scholar, James B. Angell (Michigan; 1978, 1979)

Postdoctoral Advisees

• Jonathan Lassila, Rishi Porecha, Eliza Ruben, Jason Schwans, Xue Song Shi, Sergey Solomatin, Robert Spitale

Web Site Links

• Herschlag Group Home Page

Research Interests

Our research is aimed at understanding the chemical and physical behavior underlying biological macromolecules and systems, as these behaviors define the capabilities and limitations of biology. Toward this end we study folding and catalysis by RNA, as well as catalysis by protein enzymes. Comparing and contrasting the behavior of RNA and protein systems highlights the unique features of these biological macromolecules and helps elucidate principles of folding and catalysis that may be fundamental to both class of functional macromolecules. Toward these ends, many biochemical and biophysical techniques are employed, both within the lab and through multiple collaborations. Finally, we are also involved in collaborative work with Pat Brown's lab aimed at unraveling the global logic and organization of RNA processing and organization. More detailed descriptions are available from our lab home page.

Publications

• Diverse RNA-binding proteins interact with functionally related sets of RNAs, suggesting an extensive regulatory system. Hogan DJ,  Riordan DP, Gerber AP, Herschlag D, Brown PO.  PLoS Biol.  2008; 6 (10): e255
• Comparative enzymology in the alkaline phosphatase superfamily to determine the catalytic role of an active-site metal ion. Zalatan JG,  Fenn TD, Herschlag D.  J Mol Biol.  2008; 384 (5): 1174-89
• Semiautomated and rapid quantification of nucleic acid footprinting and structure mapping experiments. Laederach A,  Das R, Vicens Q, Pearlman SM, Brenowitz M, Herschlag D, Altman RB.  Nat Protoc.  2008; 3 (9): 1395-401
• Arginine coordination in enzymatic phosphoryl transfer: evaluation of the effect of Arg166 mutations in Escherichia coli alkaline phosphatase. O'Brien PJ,  Lassila JK, Fenn TD, Zalatan JG, Herschlag D.  Biochemistry.  2008; 47 (29): 7663-72
• A repulsive field: advances in the electrostatics of the ion atmosphere. Chu VB,  Bai Y, Lipfert J, Herschlag D, Doniach S.  Curr Opin Chem Biol.  2008; 12 (6): 619-25
• Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. Hendrickson DG,  Hogan DJ, Herschlag D, Ferrell JE, Brown PO.  PLoS One.  2008; 3 (5): e2126
• Structural inference of native and partially folded RNA by high-throughput contact mapping. Das R,  Kudaravalli M, Jonikas M, Laederach A, Fong R, Schwans JP, Baker D, Piccirilli JA, Altman RB, Herschlag D.  Proc Natl Acad Sci U S A.  2008; 105 (11): 4144-9
• Coupling between ATP binding and DNA cleavage by DNA topoisomerase II: A unifying kinetic and structural mechanism. Mueller-Planitz F,  Herschlag D.  J Biol Chem.  2008; 283 (25): 17463-76
• Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs. Chu VB,  Herschlag D.  Curr Opin Struct Biol.  2008; 18 (3): 305-14
• DNA topoisomerase II selects DNA cleavage sites based on reactivity rather than binding affinity. Mueller-Planitz F,  Herschlag D.  Nucleic Acids Res.  2007; 35 (11): 3764-73
• Low specificity of metal ion binding in the metal ion core of a folded RNA. Travers KJ,  Boyd N, Herschlag D.  RNA.  2007; 13 (8): 1205-13
• Quantitative and comprehensive decomposition of the ion atmosphere around nucleic acids. Bai Y,  Greenfeld M, Travers KJ, Chu VB, Lipfert J, Doniach S, Herschlag D.  J Am Chem Soc.  2007; 129 (48): 14981-8
• Do ligand binding and solvent exclusion alter the electrostatic character within the oxyanion hole of an enzymatic active site? Sigala PA,  Fafarman AT, Bogard PE, Boxer SG, Herschlag D.  J Am Chem Soc.  2007; 129 (40): 12104-5
• Modulation of individual steps in group I intron catalysis by a peripheral metal ion. Forconi M,  Piccirilli JA, Herschlag D.  RNA.  2007; 13 (10): 1656-67
• Kinetic isotope effects for alkaline phosphatase reactions: implications for the role of active-site metal ions in catalysis. Zalatan JG,  Catrina I, Mitchell R, Grzyska PK, O'brien PJ, Herschlag D, Hengge AC.  J Am Chem Soc.  2007; 129 (31): 9789-98
• Evaluation of ion binding to DNA duplexes using a size-modified Poisson-Boltzmann theory. Chu VB,  Bai Y, Lipfert J, Herschlag D, Doniach S.  Biophys J.  2007; 93 (9): 3202-9
• Probing the origin of the compromised catalysis of E. coli alkaline phosphatase in its promiscuous sulfatase reaction. Catrina I,  O'Brien PJ, Purcell J, Nikolic-Hughes I, Zalatan JG, Hengge AC, Herschlag D.  J Am Chem Soc.  2007; 129 (17): 5760-5
• Probing the role of a secondary structure element at the 5'- and 3'-splice sites in group I intron self-splicing: the tetrahymena L-16 ScaI ribozyme reveals a new role of the G.U pair in self-splicing. Karbstein K,  Lee J, Herschlag D.  Biochemistry.  2007; 46 (16): 4861-75
• Measuring the folding transition time of single RNA molecules. Lee TH,  Lapidus LJ, Zhao W, Travers KJ, Herschlag D, Chu S.  Biophys J.  2007; 92 (9): 3275-83
• Structural transitions and thermodynamics of a glycine-dependent riboswitch from Vibrio cholerae. Lipfert J,  Das R, Chu VB, Kudaravalli M, Boyd N, Herschlag D, Doniach S.  J Mol Biol.  2007; 365 (5): 1393-406
• Interdomain communication in DNA topoisomerase II. DNA binding and enzyme activation. Mueller-Planitz F,  Herschlag D.  J Biol Chem.  2006; 281 (33): 23395-404
• Testing electrostatic complementarity in enzyme catalysis: hydrogen bonding in the ketosteroid isomerase oxyanion hole. Kraut DA,  Sigala PA, Pybus B, Liu CW, Ringe D, Petsko GA, Herschlag D.  PLoS Biol.  2006; 4 (4): e99
• Alkaline phosphatase mono- and diesterase reactions: comparative transition state analysis. Zalatan JG,  Herschlag D.  J Am Chem Soc.  2006; 128 (4): 1293-303
• Structural and functional comparisons of nucleotide pyrophosphatase/phosphodiesterase and alkaline phosphatase: implications for mechanism and evolution. Zalatan JG,  Fenn TD, Brunger AT, Herschlag D.  Biochemistry.  2006; 45 (32): 9788-803
• Promiscuous catalysis by the tetrahymena group I ribozyme. Forconi M,  Herschlag D.  J Am Chem Soc.  2005; 127 (17): 6160-1
• Dissecting eukaryotic translation and its control by ribosome density mapping. Arava Y,  Boas FE, Brown PO, Herschlag D.  Nucleic Acids Res.  2005; 33 (8): 2421-32
• Alkaline phosphatase catalysis is ultrasensitive to charge sequestered between the active site zinc ions. Nikolic-Hughes I,  O'brien PJ, Herschlag D.  J Am Chem Soc.  2005; 127 (26): 9314-5
• Determining the Mg2+ stoichiometry for folding an RNA metal ion core. Das R,  Travers KJ, Bai Y, Herschlag D.  J Am Chem Soc.  2005; 127 (23): 8272-3
• Probing counterion modulated repulsion and attraction between nucleic acid duplexes in solution. Bai Y,  Das R, Millett IS, Herschlag D, Doniach S.  Proc Natl Acad Sci U S A.  2005; 102 (4): 1035-40
• SAFA: semi-automated footprinting analysis software for high-throughput quantification of nucleic acid footprinting experiments. Das R,  Laederach A, Pearlman SM, Herschlag D, Altman RB.  RNA.  2005; 11 (3): 344-54
• Do electrostatic interactions with positively charged active site groups tighten the transition state for enzymatic phosphoryl transfer? Nikolic-Hughes I,  Rees DC, Herschlag D.  J Am Chem Soc.  2004; 126 (38): 11814-9
• Extensive association of functionally and cytotopically related mRNAs with Puf family RNA-binding proteins in yeast. Gerber AP,  Herschlag D, Brown PO.  PLoS Biol.  2004; 2 (3): E79
• A base triple in the Tetrahymena group I core affects the reaction equilibrium via a threshold effect. Karbstein K,  Tang KH, Herschlag D.  RNA.  2004; 10 (11): 1730-9
• Extraordinarily slow binding of guanosine to the Tetrahymena group I ribozyme: implications for RNA preorganization and function. Karbstein K,  Herschlag D.  Proc Natl Acad Sci U S A.  2003; 100 (5): 2300-5
• Adenosine 5'-O-(3-thio)triphosphate (ATPgammaS) is a substrate for the nucleotide hydrolysis and RNA unwinding activities of eukaryotic translation initiation factor eIF4A. Peck ML,  Herschlag D.  RNA.  2003; 9 (10): 1180-7
• The fastest global events in RNA folding: electrostatic relaxation and tertiary collapse of the Tetrahymena ribozyme. Das R,  Kwok LW, Millett IS, Bai Y, Mills TT, Jacob J, Maskel GS, Seifert S, Mochrie SG, Thiyagarajan P, Doniach S, Pollack L, Herschlag D.  J Mol Biol.  2003; 332 (2): 311-9
• Counterion distribution around DNA probed by solution X-ray scattering. Das R,  Mills TT, Kwok LW, Maskel GS, Millett IS, Doniach S, Finkelstein KD, Herschlag D, Pollack L.  Phys Rev Lett.  2003; 90 (18): 188103
• Exploration of the transition state for tertiary structure formation between an RNA helix and a large structured RNA. Bartley LE,  Zhuang X, Das R, Chu S, Herschlag D.  J Mol Biol.  2003; 328 (5): 1011-26
• Challenges in enzyme mechanism and energetics. Kraut DA,  Carroll KS, Herschlag D.  Annu Rev Biochem.  2003; 72 517-71
• Genome-wide analysis of mRNA translation profiles in Saccharomyces cerevisiae. Arava Y,  Wang Y, Storey JD, Liu CL, Brown PO, Herschlag D.  Proc Natl Acad Sci U S A.  2003; 100 (7): 3889-94
• Exploring the folding landscape of a structured RNA. Russell R,  Zhuang X, Babcock HP, Millett IS, Doniach S, Chu S, Herschlag D.  Proc Natl Acad Sci U S A.  2002; 99 (1): 155-60
• Alkaline phosphatase revisited: hydrolysis of alkyl phosphates. O'Brien PJ,  Herschlag D.  Biochemistry.  2002; 41 (9): 3207-25
• Environmental effects on phosphoryl group bonding probed by vibrational spectroscopy: implications for understanding phosphoryl transfer and enzymatic catalysis. Cheng H,  Nikolic-Hughes I, Wang JH, Deng H, O'Brien PJ, Wu L, Zhang ZY, Herschlag D, Callender R.  J Am Chem Soc.  2002; 124 (38): 11295-306
• Probing the Tetrahymena group I ribozyme reaction in both directions. Karbstein K,  Carroll KS, Herschlag D.  Biochemistry.  2002; 41 (37): 11171-83
• Dissection of a metal-ion-mediated conformational change in Tetrahymena ribozyme catalysis. Shan SO,  Herschlag D.  RNA.  2002; 8 (7): 861-72
• Precision and functional specificity in mRNA decay. Wang Y,  Liu CL, Storey JD, Tibshirani RJ, Herschlag D, Brown PO.  Proc Natl Acad Sci U S A.  2002; 99 (9): 5860-5
• Rapid compaction during RNA folding. Russell R,  Millett IS, Tate MW, Kwok LW, Nakatani B, Gruner SM, Mochrie SG, Pande V, Doniach S, Herschlag D, Pollack L.  Proc Natl Acad Sci U S A.  2002; 99 (7): 4266-71
• RNA simulations: probing hairpin unfolding and the dynamics of a GNRA tetraloop. Sorin EJ,  Engelhardt MA, Herschlag D, Pande VS.  J Mol Biol.  2002; 317 (4): 493-506
• Chemical rescue of phosphoryl transfer in a cavity mutant: a cautionary tale for site-directed mutagenesis. Admiraal SJ,  Meyer P, Schneider B, Deville-Bonne D, Janin J, Herschlag D.  Biochemistry.  2001; 40 (2): 403-13
• Defining the catalytic metal ion interactions in the Tetrahymena ribozyme reaction. Shan S,  Kravchuk AV, Piccirilli JA, Herschlag D.  Biochemistry.  2001; 40 (17): 5161-71
• Functional interrelationships in the alkaline phosphatase superfamily: phosphodiesterase activity of Escherichia coli alkaline phosphatase. O'Brien PJ,  Herschlag D.  Biochemistry.  2001; 40 (19): 5691-9
• Comparison of the hammerhead cleavage reactions stimulated by monovalent and divalent cations. O'Rear JL,  Wang S, Feig AL, Beigelman L, Uhlenbeck OC, Herschlag D.  RNA.  2001; 7 (4): 537-45
• Probing the folding landscape of the Tetrahymena ribozyme: commitment to form the native conformation is late in the folding pathway. Russell R,  Herschlag D.  J Mol Biol.  2001; 308 (5): 839-51
• The P5abc peripheral element facilitates preorganization of the tetrahymena group I ribozyme for catalysis. Engelhardt MA,  Doherty EA, Knitt DS, Doudna JA, Herschlag D.  Biochemistry.  2000; 39 (10): 2639-51
• Small angle X-ray scattering reveals a compact intermediate in RNA folding. Russell R,  Millett IS, Doniach S, Herschlag D.  Nat Struct Biol.  2000; 7 (5): 367-70
• Use of duplex rigidity for stability and specificity in RNA tertiary structure. Narlikar GJ,  Bartley LE, Herschlag D.  Biochemistry.  2000; 39 (20): 6183-9
• A single-molecule study of RNA catalysis and folding. Zhuang X,  Bartley LE, Babcock HP, Russell R, Ha T, Herschlag D, Chu S.  Science.  2000; 288 (5473): 2048-51
• An unconventional origin of metal-ion rescue and inhibition in the Tetrahymena group I ribozyme reaction. Shan SO,  Herschlag D.  RNA.  2000; 6 (6): 795-813
• Specificity from steric restrictions in the guanosine binding pocket of a group I ribozyme. Russell R,  Herschlag D.  RNA.  1999; 5 (2): 158-66
• Catalytic promiscuity and the evolution of new enzymatic activities. O'Brien PJ,  Herschlag D.  Chem Biol.  1999; 6 (4): R91-R105
• Nucleophilic activation by positioning in phosphoryl transfer catalyzed by nucleoside diphosphate kinase. Admiraal SJ,  Schneider B, Meyer P, Janin J, Véron M, Deville-Bonne D, Herschlag D.  Biochemistry.  1999; 38 (15): 4701-11
• Probing the role of metal ions in RNA catalysis: kinetic and thermodynamic characterization of a metal ion interaction with the 2'-moiety of the guanosine nucleophile in the Tetrahymena group I ribozyme. Shan SO,  Herschlag D.  Biochemistry.  1999; 38 (34): 10958-75
• Protonated 2'-aminoguanosine as a probe of the electrostatic environment of the active site of the Tetrahymena group I ribozyme. Shan SO,  Narlikar GJ, Herschlag D.  Biochemistry.  1999; 38 (34): 10976-88
• Hydrogen bonding in enzymatic catalysis: analysis of energetic contributions. Shan SO,  Herschlag D.  Methods Enzymol.  1999; 308 246-76
• New pathways in folding of the Tetrahymena group I RNA enzyme. Russell R,  Herschlag D.  J Mol Biol.  1999; 291 (5): 1155-67
• Three metal ions at the active site of the Tetrahymena group I ribozyme. Shan S,  Yoshida A, Sun S, Piccirilli JA, Herschlag D.  Proc Natl Acad Sci U S A.  1999; 96 (22): 12299-304
• Stereospecificity of reactions catalyzed by HIV-1 integrase. Gerton JL,  Herschlag D, Brown PO.  J Biol Chem.  1999; 274 (47): 33480-7
• Characterization of a local folding event of the Tetrahymena group I ribozyme: effects of oligonucleotide substrate length, pH, and temperature on the two substrate binding steps. Narlikar GJ,  Bartley LE, Khosla M, Herschlag D.  Biochemistry.  1999; 38 (43): 14192-204
• Identification of the hammerhead ribozyme metal ion binding site responsible for rescue of the deleterious effect of a cleavage site phosphorothioate. Wang S,  Karbstein K, Peracchi A, Beigelman L, Herschlag D.  Biochemistry.  1999; 38 (43): 14363-78
• Kinetic dissection of fundamental processes of eukaryotic translation initiation in vitro. Lorsch JR,  Herschlag D.  EMBO J.  1999; 18 (23): 6705-17
• Effects of oligonucleotide length and atomic composition on stimulation of the ATPase activity of translation initiation factor elF4A. Peck ML,  Herschlag D.  RNA.  1999; 5 (9): 1210-21
• The DEAD box protein eIF4A. 1. A minimal kinetic and thermodynamic framework reveals coupled binding of RNA and nucleotide. Lorsch JR,  Herschlag D.  Biochemistry.  1998; 37 (8): 2180-93
• The DEAD box protein eIF4A. 2. A cycle of nucleotide and RNA-dependent conformational changes. Lorsch JR,  Herschlag D.  Biochemistry.  1998; 37 (8): 2194-206
• Direct demonstration of the catalytic role of binding interactions in an enzymatic reaction. Narlikar GJ,  Herschlag D.  Biochemistry.  1998; 37 (28): 9902-11
• A core folding model for catalysis by the hammerhead ribozyme accounts for its extraordinary sensitivity to abasic mutations. Peracchi A,  Karpeisky A, Maloney L, Beigelman L, Herschlag D.  Biochemistry.  1998; 37 (42): 14765-75
• Structure-function relationships in the hammerhead ribozyme probed by base rescue. Peracchi A,  Matulic-Adamic J, Wang S, Beigelman L, Herschlag D.  RNA.  1998; 4 (11): 1332-46
• Involvement of a specific metal ion in the transition of the hammerhead ribozyme to its catalytic conformation. Peracchi A,  Beigelman L, Scott EC, Uhlenbeck OC, Herschlag D.  J Biol Chem.  1997; 272 (43): 26822-6
• Quantitating tertiary binding energies of 2' OH groups on the P1 duplex of the Tetrahymena ribozyme: intrinsic binding energy in an RNA enzyme. Narlikar GJ,  Khosla M, Usman N, Herschlag D.  Biochemistry.  1997; 36 (9): 2465-77
• Mechanistic aspects of enzymatic catalysis: lessons from comparison of RNA and protein enzymes. Narlikar GJ,  Herschlag D.  Annu Rev Biochem.  1997; 66 19-59
• Isolation of a local tertiary folding transition in the context of a globally folded RNA. Narlikar GJ,  Herschlag D.  Nat Struct Biol.  1996; 3 (8): 701-10
• Ras-catalyzed hydrolysis of GTP: a new perspective from model studies. Maegley KA,  Admiraal SJ, Herschlag D.  Proc Natl Acad Sci U S A.  1996; 93 (16): 8160-6
• Rescue of abasic hammerhead ribozymes by exogenous addition of specific bases. Peracchi A,  Beigelman L, Usman N, Herschlag D.  Proc Natl Acad Sci U S A.  1996; 93 (21): 11522-7
• The change in hydrogen bond strength accompanying charge rearrangement: implications for enzymatic catalysis. Shan SO,  Herschlag D.  Proc Natl Acad Sci U S A.  1996; 93 (25): 14474-9
• Mechanistic investigations of a ribozyme derived from the Tetrahymena group I intron: insights into catalysis and the second step of self-splicing. Mei R,  Herschlag D.  Biochemistry.  1996; 35 (18): 5796-809
• pH dependencies of the Tetrahymena ribozyme reveal an unconventional origin of an apparent pKa. Knitt DS,  Herschlag D.  Biochemistry.  1996; 35 (5): 1560-70
• The energetics of hydrogen bonds in model systems: implications for enzymatic catalysis. Shan SO,  Loh S, Herschlag D.  Science.  1996; 272 (5258): 97-101
• Mapping the transition state for ATP hydrolysis: implications for enzymatic catalysis. Admiraal SJ,  Herschlag D.  Chem Biol.  1995; 2 (11): 729-39
• RNA chaperones and the RNA folding problem. Herschlag D,  J Biol Chem.  1995; 270 (36): 20871-4
• Use of binding energy by an RNA enzyme for catalysis by positioning and substrate destabilization. Narlikar GJ,  Gopalakrishnan V, McConnell TS, Usman N, Herschlag D.  Proc Natl Acad Sci U S A.  1995; 92 (9): 3668-72
• The nature of the transition state for enzyme-catalyzed phosphoryl transfer. Hydrolysis of O-aryl phosphorothioates by alkaline phosphatase. Hollfelder F,  Herschlag D.  Biochemistry.  1995; 34 (38): 12255-64
• An RNA chaperone activity of non-specific RNA binding proteins in hammerhead ribozyme catalysis. Herschlag D,  Khosla M, Tsuchihashi Z, Karpel RL.  EMBO J.  1994; 13 (12): 2913-24
• Dissection of the role of the conserved G.U pair in group I RNA self-splicing. Knitt DS,  Narlikar GJ, Herschlag D.  Biochemistry.  1994; 33 (46): 13864-79
• Comparison of pH dependencies of the Tetrahymena ribozyme reactions with RNA 2'-substituted and phosphorothioate substrates reveals a rate-limiting conformational step. Herschlag D,  Khosla M.  Biochemistry.  1994; 33 (17): 5291-7
• The importance of being ribose at the cleavage site in the Tetrahymena ribozyme reaction. Herschlag D,  Eckstein F, Cech TR.  Biochemistry.  1993; 32 (32): 8312-21
• Synergism in transcriptional activation: a kinetic view. Herschlag D,  Johnson FB.  Genes Dev.  1993; 7 (2): 173-9
• Contributions of 2'-hydroxyl groups of the RNA substrate to binding and catalysis by the Tetrahymena ribozyme. An energetic picture of an active site composed of RNA. Herschlag D,  Eckstein F, Cech TR.  Biochemistry.  1993; 32 (32): 8299-311
• Protein enhancement of hammerhead ribozyme catalysis. Tsuchihashi Z,  Khosla M, Herschlag D.  Science.  1993; 262 (5130): 99-102