Research Interests:

• Crystallography
• Protein Folding
• Bioinformatics
• Chromatin and chromosome structure

Crystallography is the primary method employed to determine
3-dimensional structures of large biological molecules, namely proteins and nucleic acids.

The principal tool for studying single crystals is Xray diffraction, which yields an image of a molecule's electron density, or more precisely, an average electron density of all the molecules in
the crystal. The average electron density contains not only
the information about the position of atoms, but also information about the possible spread of atomic positions.

The range of protein motions in the crystal is a dynamic property that can be studied by Xray diffraction. The difficulty is not in generating possible solutions to the problem, but rather in estimating the reliability of the result. Mathematically, the above problem is related to the "phase problem" in X-ray diffraction.

Our research addresses all aspects of phase estimates through interference measurements, direct methods, and dynamic simulations in the crystal lattice.

The methods for the generation of a 3-dimensional molecular image will combine diverse sources of information, namely experimental (e.g., Multiple Anomalous Diffraction) and theoretical (predictions
of the expected result). This combined process has mathematical similarity to the process of automated reasoning and pattern recognition.

The particular biological process of interest to this laboratory
is protein folding. Proteins function in the globular, folded state;
but they are produced in the elongated, unfolded state. For many proteins, the transition to folded state is accomplished with help from chaperonin proteins. Understanding the structure and function of the 800 kilodalton chaperonin GroEL requires finding out how
this chaperonin can bind a large class of unfolded proteins.
The structural challenge is to explain how a disordered state can
be bound specifically.

• Rezacova, P., Borek, D., Moy, S.F., Joachimiak, A., Otwinowski, Z. (2008)
  Crystal structure and putative function of small Toprim domain-containing protein from Bacillus stearothermophilus.
  Proteins 70: 311-9. Link
• Kudlicki, A., Rowicka, M., Otwinowski, Z. (2007)
  The crystallographic fast Fourier transform. Recursive symmetry reduction.
  Acta Crystallogr. A 63: 465-80. pdf
• Machius, M., Brautigam, C.A., Tomchick, D.R., Ward, P., Otwinowski, Z., Blevins, J.S., Deka, R.K., Norgard, M.V. (2007)
  Structural and biochemical basis for polyamine binding to the Tp0655 lipoprotein of Treponema pallidum: putative role for Tp0655 (TpPotD) as a polyamine receptor.
  J. Mol. Biol. 373: 681-94. pdf
• Rowicka, M., Kudlicki, A., Tu, B.P., Otwinowski, Z. (2007)
  High-resolution timing of cell cycle-regulated gene expression.
  Proc. Natl. Acad. Sci. U.S.A. 104: 16892-7. Link
• Rezacova, P., Krejcirikova, V., Borek, D., Moy, S.F., Joachimiak, A., Otwinowski, Z. (2007)
  The crystal structure of the effector-binding domain of the trehalose repressor TreR from Bacillus subtilis 168 reveals a unique quarternary assembly.
  Proteins 69: 679-82. Link
• Grabowski, M., Joachimiak, A., Otwinowski, Z., Minor, W. (2007)
  Structural genomics: keeping up with expanding knowledge of the protein universe.
  Curr. Opin. Struct. Biol. 17: 347-53. Link
• Kudlicki, A., Rowicka, M., Otwinowski, Z. (2007)
  SCEPTRANS: an online tool for analyzing periodic transcription in yeast.
  Bioinformatics 23: 1559-61. Link
• Borek, D., Ginell, S.L., Cymborowski, M., Minor, W., Otwinowski, Z. (2007)
  The many faces of radiation-induced changes. pdf
  J. Synchrotron. Radiat. 14: 24-33.
• Yang, M., Gocke, C.B., Luo, X., Borek, D., Tomchick., D.R., Machius, M., Otwinowski, Z., Yu, H. (2006)
  Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase. Link
  Mol. Cell. 23: 377-87.
• Minor, W., Cymborowski, M., Otwinowski, Z., Chruszcz, M. (2006)
  HKL-3000: the integration of data reduction and structure solution-from diffraction images to an initial model in minutes.
  Acta Crystallogr. D 62: 859-66. pdf
• Pertsemlidis, A., Zelinka, J., Fondon, J.W. 3rd, Henderson, R.K., Otwinowski, Z. (2005)
  Bayesian statistical studies of the Ramachandran distribution.
  Stat. Appl. Genet. Mol. Biol. 4: Article 35. Link
• Stefankova, P., Maderova, J., Barak, I., Kollarova, M., Otwinowski, Z. (2005)
  Expression, purification and X-ray crystallographic analysis of thioredoxin from Streptomyces coelicolor.
  Acta Crystallogr. F 61: 164-8. Link
• Cigler, P., Kozisek, M., Rezacova, P., Brynda, J., Otwinowski, Z., Pokorna, J., Plesek, J., Gruner, B., Doleckova-Maresova, L., Masa, M., Sedlacek, J., Bodem, J., Krausslich, H.G., Kral, V., Konvalinka, J. (2005)
  From nonpeptide toward noncarbon protease inhibitors: metallacarboranes as specific and potent inhibitors of HIV protease.
  Proc. Natl. Acad. Sci. U.S.A. 102: 15394-9. Link
• Kudlicki, A., Rowicka, M., Otwinowski, Z.(2004)
  Stereochemical Rules for Connecting Disjoint Protein Fragments
  AIP Conference Proceedings 735, 169. pdf
• Rowicka, M., Kudlicki, A., Zelinka, J., Otwinowski, Z. (2004)
  Coordinate transformations in modern crystallographic computing.
  Acta Crystallogr. A 60: 542-9. pdf
• O'Toole, N., Grabowski, M., Otwinowski, Z., Minor, W., Cygler, M. (2004)
  The structural genomics experimental pipeline: insights from global target lists.
  Proteins 56: 201-10. Link
• Kudlicki, A., Rowicka, M., Otwinowski, Z. (2004)
  The crystallographic fast Fourier transform. IV. FFT-asymmetric units in the reciprocal space.
  Acta Crystallogr. A 60: 146-52. pdf
• Borek, D., Minor, W., Otwinowski, Z. (2003)
  Measurement errors and their consequences in protein crystallography.
  Acta Crystallogr. D 59: 2031-8. Link
• Otwinowski, Z., Borek, D., Majewski, W., Minor, W. (2003)
  Multiparametric scaling of diffraction intensities.
  Acta Crystallogr. A 59: 228-34. pdf
• Rowicka, M., Kudlicki, A., Otwinowski, Z. (2003)
  The crystallographic fast Fourier transform. III. Centred lattices.
  Acta Crystallogr. A 59: 183-92. pdf
• Rowicka, M., Kudlicki, A., Otwinowski, Z. (2003)
  The crystallographic fast Fourier transform. II. One-step symmetry reduction.
  Acta Crystallogr. A 59: 172-82. pdf
• Rowicka, M., Kudlicki, A., Otwinowski, Z. (2002)
  The crystallographic fast Fourier transform. I. p3 symmetry.
  Acta Crystallogr. A 58: 574-9. pdf
• Pavelcik, F., Zelinka, J., Otwinowski, Z. (2002)
  Methodology and applications of automatic electron-density map interpretation by six-dimensional rotational and translational search for molecular fragments.
  Acta Crystallogr. D 58: 275-83. pdf
• Taylor, A.B., Smith, B.S., Kitada, S., Kojima, K., Miyaura, H., Otwinowski, Z., Ito, A., Deisenhofer, J. (2001)
  Crystal structures of mitochondrial processing peptidase reveal the mode for specific cleavage of import signal sequences.
  Structure 9: 615-25. pdf
• Korolev, S., Dementieva, I., Sanishvili, R., Minor, W., Otwinowski, Z., Joachimiak, A. (2001)
  Using surface-bound rubidium ions for protein phasing.
  Acta Crystallogr. D 57: 1008-12. Link
• Minor, W., Tomchick, D., Otwinowski, Z. (2000)
  Strategies for macromolecular synchrotron crystallography.
  Structure 8: R105-10. Link
• Walsh, M.A., Otwinowski, Z., Perrakis, A., Anderson, P.M., Joachimiak, A. (2000)
  Structure of cyanase reveals that a novel dimeric and decameric arrangement of subunits is required for formation
  of the enzyme active site.
  Structure 8: 505-14. Link
• Minor, W., Steczko, J., Stec, B., Otwinowski, Z., Bolin, J.T., Walter, R., Axelrod, B. (1996)
  Crystal structure of soybean lipoxygenase L-1 at 1.4 A resolution.
  Biochemistry 35: 10687-701. Link
• Boisvert, D.C., Wang, J., Otwinowski, Z., Horwich, A.L., Sigler, P.B. (1996)
  The 2.4 A crystal structure of the bacterial chaperonin GroEL complexed with ATP gamma S.
  Nat. Struct. Biol. 3: 170-7. pdf
• Zhang, R.G., Westbrook, M.L., Westbrook, E.M., Scott, D.L., Otwinowski, Z., Maulik, P.R., Reed, R.A., Shipley, G.G. (1995)
  The 2.4 A crystal structure of cholera toxin B subunit pentamer: choleragenoid.
  J. Mol. Biol. 251: 550-62. Link
• Braig, K., Otwinowski, Z., Hegde, R., Boisvert, D.C., Joachimiak, A., Horwich, A.L., Sigler, P.B. (1994)
  The crystal structure of the bacterial chaperonin GroEL at 2.8 A.
  Nature 371: 578-86. Link
• Minor, W., Steczko, J., Bolin, J.T., Otwinowski, Z., Axelrod, B. (1993)
  Crystallographic determination of the active site iron and its ligands in soybean lipoxygenase L-1.
  Biochemistry 32: 6320-3. Link
• Luisi, B.F., Xu, W.X., Otwinowski, Z., Freedman, L.P., Yamamoto, K.R., Sigler, P.B. (1991)
  Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA.
  Nature 352: 497-505. Link
• Scott, D.L., Otwinowski, Z., Gelb, M.H., Sigler, P.B. (1990)
  Crystal structure of bee-venom phospholipase A2 in a complex with a transition-state analogue.
  Science 250: 1563-6. Erratum in: Science (1991) 252: 764. Link
• White, S.P., Scott, D.L., Otwinowski, Z., Gelb, M.H., Sigler, P.B. (1990)
  Crystal structure of cobra-venom phospholipase A2 in a complex with a transition-state analogue.
  Science 250: 1560-3. Link
• Scott, D.L., White, S.P., Otwinowski, Z., Yuan, W., Gelb, M.H., Sigler, P.B. (1990)
  Interfacial catalysis: the mechanism of phospholipase A2.
  Science 250: 1541-6. Link
• Otwinowski, Z., Schevitz, R.W., Zhang, R.G., Lawson, C.L., Joachimiak, A., Marmorstein, R.Q., Luisi, B.F., Sigler, P.B. (1988)
  Crystal structure of trp repressor/operator complex at atomic resolution.
  Nature 335: 321-9. Erratum in: Nature (1988) 335: 837. Link
• Lawson, C.L., Zhang, R.G., Schevitz, R.W., Otwinowski, Z., Joachimiak, A., Sigler, P.B. (1988)
  Flexibility of the DNA-binding domains of trp repressor.
  Proteins 3: 18-31. Link
• Zhang, R.G., Joachimiak, A., Lawson, C.L., Schevitz, R.W., Otwinowski, Z., Sigler, P.B. (1987)
  The crystal structure of trp aporepressor at 1.8 A shows how binding tryptophan enhances DNA affinity.
  Nature 327: 591-7. Link
• Achari, A., Scott, D., Barlow, P., Vidal, J.C., Otwinowski, Z., Brunie, S., Sigler, P.B. (1987)
  Facing up to membranes: structure/function relationships in phospholipases.
  Cold Spring Harb. Symp. Quant. Biol. 52: 441-52. Link
• Schevitz, R.W., Otwinowski, Z., Joachimiak, A., Lawson, C.L., Sigler, P.B. (1985)
  The three-dimensional structure of trp repressor.
  Nature 317: 782-6. Link
• Abrosimov, A.T., Bellini, G., Chernenko, I.P., Dicorato, M., Drondina, G.I., Frabetti, P.L., Ivanshin, Y,I., Laurikainen, P., Litkin, l.K., Lobanova, V.P., Meroni, E., Micheletti, S., Moiseenko, V.A., Nikanorov, V.I., Otwinowski, S., Otwinowski, Z., Palombo, F., Pernicka, M., Pisarev, A.F., Rancoita, P.G., Sala, S., Sychkov, S.I., Szeptycka, M., Tjapkin, A.A., Vasilevski, I.M., Vegni, G., Vishevskaja, K.P., Vishnjakov, V.V., Wojcik, W., Zaimidoroga, O.A. (1979)
  Multiplicity of charged-particles in pi-interactions on nuclei at 40-GEV-C
  Nuclear Physics B 158 (1) 11-28. Link