This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. DNA rearrangement/recombination enzymes alter covalent structure of DNA, by cleaving and rejoining DNA strands. These proteins play important roles in diverse biological contexts, including viral integration into host's genome, maintenance of chromosome integrity, and generation of genetic diversity. Using x-ray crystallography, we are studying three distinct classes of DNA rearrangement enzymes to better understand how these enzymes function. The first class is the retroviral integrase. Retroviruses, including HIV-1 that causes AIDS, have an RNA genome that is reverse-transcribed into a linear viral DNA upon entering the host cell. Integration of this viral DNA into host's chromosome is an essential step in the lifecycle of retroviruses, and is carried out by the virally encoded integrase (IN) protein. We are pursuing crystal structures of the functional 3-domain IN protein as well as IN-DNA complexes, using IN from HIV and RSV (Rous Sarcoma Virus) systems. The second class is the DNA resolvase involved in the maintenance of bacterial linear chromosomes. Some bacterial pathogens, including the Lyme disease spirochete Borrelia burgdorferi, have linear chromosomes with covalently closed hairpin termini. Replication of such linear chromosomes requires resolution of a catenated circular intermediate into unit-length chromosomes, which is carried out by the hairpin-forming DNA resolvase enzyme. Using Borrelia and Agrobacterium systems, we are determining crystal structures of the resolvase-DNA complexes to gain insights into the mechanism of DNA strand cleavages and subsequent hairpin formation. The third class is the Holliday junction resolvase involved in resolution of the cruciform-shaped DNA recombination intermediates. We are pursuing crystal structure of the poxvirus HJ resolvase in complex with HJ DNA substrates. If successful, it will be the first atomic structure of an enzyme-DNA complex for the large family of HJ resolvases represented by E. coli RuvC.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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Cornell University
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Fallas, Jorge A; Ueda, George; Sheffler, William et al. (2017) Computational design of self-assembling cyclic protein homo-oligomers. Nat Chem 9:353-360
Krotee, Pascal; Rodriguez, Jose A; Sawaya, Michael R et al. (2017) Atomic structures of fibrillar segments of hIAPP suggest tightly mated ?-sheets are important for cytotoxicity. Elife 6:
Dhayalan, Balamurugan; Mandal, Kalyaneswar; Rege, Nischay et al. (2017) Scope and Limitations of Fmoc Chemistry SPPS-Based Approaches to the Total Synthesis of Insulin Lispro via Ester Insulin. Chemistry 23:1709-1716
Bale, Jacob B; Gonen, Shane; Liu, Yuxi et al. (2016) Accurate design of megadalton-scale two-component icosahedral protein complexes. Science 353:389-94
AhYoung, Andrew P; Koehl, Antoine; Vizcarra, Christina L et al. (2016) Structure of a putative ClpS N-end rule adaptor protein from the malaria pathogen Plasmodium falciparum. Protein Sci 25:689-701
Hancock, Stephen P; Stella, Stefano; Cascio, Duilio et al. (2016) DNA Sequence Determinants Controlling Affinity, Stability and Shape of DNA Complexes Bound by the Nucleoid Protein Fis. PLoS One 11:e0150189
Taylor, Noah D; Garruss, Alexander S; Moretti, Rocco et al. (2016) Engineering an allosteric transcription factor to respond to new ligands. Nat Methods 13:177-83
Kattke, Michele D; Chan, Albert H; Duong, Andrew et al. (2016) Crystal Structure of the Streptomyces coelicolor Sortase E1 Transpeptidase Provides Insight into the Binding Mode of the Novel Class E Sorting Signal. PLoS One 11:e0167763
Jorda, J; Leibly, D J; Thompson, M C et al. (2016) Structure of a novel 13 nm dodecahedral nanocage assembled from a redesigned bacterial microcompartment shell protein. Chem Commun (Camb) 52:5041-4
Dhayalan, Balamurugan; Fitzpatrick, Ann; Mandal, Kalyaneswar et al. (2016) Efficient Total Chemical Synthesis of (13) C=(18) O Isotopomers of Human Insulin for Isotope-Edited FTIR. Chembiochem 17:415-20

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