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Open Access Publications from the University of California

Scholarly Works (3 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2023)

Viroporins are small multifunctional proteins that modify cellular membranes to facilitate viral infections such as viral nucleic acid entry and the release of virions from infected cells. We are interested in studying the evolutionary relationships among these proteins, in particular their organization into families and superfamilies. Comparative genomics analysis of 120 viral genomes, using the Phylogenetic Profiles method, allowed the identification of 12 families organized in four groups of functionally related families. Additionally, we compiled a list of 50 families from the Transporter Classification Database (TCDB) with viroporin-like attributes (i.e., length ≤ 300 aas, similar topology and/or documented viroporin activity). We then used TCDB as reference to search for homology signals among all 59 families using bioinformatic methods published by the Saier lab. These include (1) sequence similarity, (2) compatibility of topology and hydropathy profiles, (3) similarity of sequence profiles from multiple sequence alignments, (4) shared motifs, and (5) conserved domains. We were able to infer homology among 17 families, some of which expand the established Viral Envelope Fusion Protein Superfamily to include 7 families (TC: 1.G.9, 1.A.58, 1.A.19, 1.G.7, 1.A.40, 1.A.41 and 1.G.13), and the rest constitute three novel superfamilies: Viroporin-1 consists of three families (TC: 1.A.92, 1.A.93, and 1.A.94); Viroporin-2 is composed of two functionally-linked families (TC: 1.A.57 and 1.A.117); Viroporin-3 is composed of 3 functionally-related families (TC: 1.A.65, 1.A.99, and 1.A.116). We are confident that these results will be useful to the research community.

    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2017)
    The oxo-cobalt cubane unit [Co4O4] is of interest as a homogeneous oxygen-evolution reaction (OER) catalyst, and as a functional mimic of heterogeneous cobalt oxide OER catalysts. The synthesis of several new cubanes allows evaluation of redox potentials for the [Co4O4] cluster, which are highly sensitive to the ligand environment and span a remarkable range of 1.42 V. The [CoIII4O4]4+/[CoIII3CoIVO4]5+ and [CoIII3CoIVO4]5+/[CoIII2CoIV2O4]6+ redox potentials are reliably predicted by the pKas of the ligands. Hydrogen bonding is also shown to significantly raise the redox potentials, by ∼500 mV. The potential-pKa correlation is used to evaluate the feasibility of various proposed OER catalytic intermediates, including high-valent Co-oxo species. The synthetic methods and structure-reactivity relationships developed by these studies should better guide the design of new cubane-based OER catalysts.
      Cover page: Synthetic control and empirical prediction of redox potentials for Co 4 O 4 cubanes over a 1.4 V range: implications for catalyst design and evaluation of high-valent intermediates in water oxidation
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2021)
      Enzymes in multistep metabolic pathways utilize an array of regulatory mechanisms to maintain a delicate homeostasis [K. Magnuson, S. Jackowski, C. O. Rock, J. E. Cronan, Jr, Microbiol. Rev. 57, 522-542 (1993)]. Carrier proteins in particular play an essential role in shuttling substrates between appropriate enzymes in metabolic pathways. Although hypothesized [E. Płoskoń et al., Chem. Biol. 17, 776-785 (2010)], allosteric regulation of substrate delivery has never before been demonstrated for any acyl carrier protein (ACP)-dependent pathway. Studying these mechanisms has remained challenging due to the transient and dynamic nature of protein-protein interactions, the vast diversity of substrates, and substrate instability [K. Finzel, D. J. Lee, M. D. Burkart, ChemBioChem 16, 528-547 (2015)]. Here we demonstrate a unique communication mechanism between the ACP and partner enzymes using solution NMR spectroscopy and molecular dynamics to elucidate allostery that is dependent on fatty acid chain length. We demonstrate that partner enzymes can allosterically distinguish between chain lengths via protein-protein interactions as structural features of substrate sequestration are translated from within the ACP four-helical bundle to the protein surface, without the need for stochastic chain flipping. These results illuminate details of cargo communication by the ACP that can serve as a foundation for engineering carrier protein-dependent pathways for specific, desired products.
        Cover page: Decoding allosteric regulation by the acyl carrier protein
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