Research:
Decoding the internal workings of the protein assemblies that catalyze complex biological functions remains the imperative of structural molecular biology. Accomplishing this goal will require study of ever-larger molecular assemblies chosen to answer specific biochemical questions. The biological systems that I have selected for initial study are the nucleo-protein assemblies that are formed at the sites of the initiation of DNA replication. Accurate replication of DNA is mediated by multi-protein assemblies that initiate DNA synthesis, elongate daughter strands, and assure the integrity of the catalyzed chemical reactions. We will use X-ray crystallography to determine the structure of selected functionally relevant assemblies with the goal of understanding biochemical data present in these systems. Structure determinations will be followed by functional studies of designed variants of these assemblies to test models of biochemical function. While the primary goal of this work will be to decipher biological function, studies of these assemblies are expected to provide the added benefit of making available much-needed targets for structure-based design of antibiotics and anti-cancer therapeutics.
Selected Publications: Samuels M., Gulati G., Shin JH, Opara R, McSweeney E, Sekedat M, Long S, Kelman Z and Jeruzalmi D. A biochemically active MCM-like helicase in Bacillus cereus. Nucleic Acids Res. 2009 Jul;37(13):4441-52 Pakotiprapha D, Liu Y, Verdine, GL, Jeruzalmi D. A structural model for the damage-sensing complex in bacterial nucleotide excision repair. J Biol Chem. 2009 May 8;284(19):12837-44. Jeruzalmi, D. Enzymatic Synthesis of Multimilligram Quantities of Large Linear DNA Molecules for Structural Studies. Cold Spring Harbor Protocols, Cold Spring Harb. Protoc.; 2009; doi:10.1101/pdb.prot5197. Muecke M., Davey M., and Jeruzalmi D. Enzymatic Synthesis of Large Linear DNA Molecules for Structural and Biochemical Studies. Structure, Volume 16, Issue 6, 11 June 2008, Pages 837-841 Pakotiprapha D, Inuzuka Y, Bowman BR, Moolenaar GF, Goosen N, Jeruzalmi D., Verdine GL. Crystal structure of Bacillus stearothermophilus UvrA provides insight into ATP-modulated dimerization, UvrB interaction, and DNA binding. Mol Cell. 2008 Jan 18;29(1):122-33. Jeruzalmi, D. (2007) First analysis of macromolecular crystals: biochemistry and x-ray diffraction. Methods Mol Biol. 2007;364:43-62 O’Donnell, M., and Jeruzalmi, D., (2006) Helical Proteins Initiate Replication of DNA Helices. NSMB 13:665-667 Jeruzalmi, D., (2005) The Opened Processivity Clamp Slides into View. Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):14939-40. Jeruzalmi, D., (2004) Chromosomal DNA replication on a protein "chip". Structure, 12:2100-2. Jeruzalmi, D., O’Donnell, M., and Kuriyan, J. (2002) Clamp Loaders and Sliding Clamps. Curr Opin Struct Biol, 12:217-24. Bruck I., Yuzhakov A., Yurieva O., Jeruzalmi D., Skangalis M., Kuriyan J., O'Donnell M. (2002) Analysis of a multicomponent thermostable DNA polymerase III replicase from an extreme thermophile. J Biol Chem 277:17334-48 Jeruzalmi, D., O’Donnell, M., and Kuriyan, J. (2001) Crystal Structure of the Processivity Clamp Loader Gamma (g) Complex of E. coli DNA Polymerase III. Cell, 106, 429-441. Jeruzalmi, D., Yurieva, O., Zhao, Y., Young, M., Stewart, J., Hingorani, M., O’Donnell, M., and Kuriyan, J. (2001) Mechanism of Processivity Clamp Opening by the Delta Subunit Wrench of the Clamp Loader Complex of E. coli DNA Polymerase III. Cell, 106, 417-428. Moarefi, I., Jeruzalmi, D., Turner, J., and Kuriyan, J. (2000) Crystal Structure of the DNA Polymerase Processivity Factor of T4 Bacteriophage. J Mol Biol, 274, 748-756. Cheetham, G. M. T., Jeruzalmi, D. and Steitz, T. A. (1999) Structural basis for initiation of transcription provided by an RNA polymerase-promoter complex. Nature, 399, 80-83. Jeruzalmi, D. and Steitz, T. A. (1998) Structure of T7 RNA polymerase complexed to the transcriptional inhibitor T7 lysozyme. EMBO J, 17, 4101-4113. |
