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Department of Pharmacy and Biotechnology - FABIT

Laboratory of Bioinorganic Chemistry. Coordinator: Ciurli

The main goal of the research is determination, at the molecular and structural level, of the structure-dynamic-function relationships of enzymes and other proteins involved in critical metabolic processes in the areas of human health and the environment, and their interactions with other proteins, nucleic acids, drugs, or metal ions.

Areas: Cancer biology Drug discovery and development Industrial, plant and environmental biotechnologies
Fig.1: Examples of proteins studied in the Laboratory of Bioinorganic Chemistry and some of the techniques used.

Research Themes

  1. The study of the structure and chemistry of urease, an enzyme containing nickel that catalyzes the hydrolysis of urea to yield ammonium and bicarbonate ions in the last stage of organic nitrogen biomineralization. Urease inhibitors can increase the efficiency of nitrogen fertilization with urea and to decrease the negative effects of the infections of the gastrointestinal and urinary system by ureolytic pathogenic bacteria. The design of efficient inhibitors, and having minimal environmental and human impact, requires the molecular structure of the active site for the structure-based molecular design.
  2. The study of the accessory proteins of urease, necessary for the transport of Ni(II) (UreE) and for the in vivo assembly of the metal site (UreD, UreF, UreG) of urease is an important theme of our group, as it represents a new possibility of identifying new possible targets for drug design. The identification of the structure of these proteins and their interactions, in the presence and absence of Ni(II) and other cofactors, is necessary to understand their operating mechanism and therefore its modulation, possibly inhibiting it with specific molecules.
  3. Nichel homeostasis in bacteria is studied on a transcriptional level, through the determination of the structure-functions relationships of transcriptional metal dependent regulators (NikR, RcnR, SrnR) and of Ni(II) membrane transporters (NixA).
  4.  Nickel is a Class 1 carcinogen in nasal and lung tissues and is an important environmental pollutant, found in fine powders resulting from air pollution. The molecular mechanisms underlying its carcinogenicity are still unknown. Through the study of nickel-binding proteins involved in lung tumor development, such as NDRG1, we seek to understand how nickel acts at the cellular level to induce cell transformation. This understanding is crucial for designing molecules that can prevent or treat this type of tumor.
  5. Structure-function relationships studies of viral proteases from SARS-CoV-2, Dengue virus, and West Nile virus. The research focuses on conducting structural and kinetic studies of viral proteases activity and their inhibition, with the aim of identifying new molecules as potential drugs. The research is carried out in collaboration with scientists from the Rensselaer Polytechnic Institute (Troy, NY, USA).
  6. Finally, a line of research has recently been opened to study the structure-function relationship of pathogenic variants of proteins essential for cellular respiration, such as complex I and complex III.

For additional information, visit our website.

Fig.2: Word cloud representing the publications of the Bioinorganic Chemistry Laboratory

Lab Members

Stefano Ciurli,  Full Professor

Francesco Musiani,  Associate Professor

Barbara Zambelli,  Associate Professor

Luca Mazzei,  Tenur Track Assistant Professor

Laura Rigobello, PhD Student

Giorgia Frumenzio, PhD Student

Claudio Pino, PhD Student

Noemi Carosella, PhD Student

Sofia Ranieri, PhD Student

Job Openings or Internship Projects

Please visit Prof. Stefano Ciurli,  Francesco Musiani, Barbara Zambelli personal website and our group website .

Main publications

  • L. Mazzei;* S. Ranieri; D. Silvestri; R. Greene-Cramer; C. Cioffi; G. T. Montelione; S. Ciurli* “An isothermal calorimetry assay for determining steady state kinetic and Ensitrelvir inhibition parameters for SARS-CoV-2 3CL-protease” 2024, Nature Sci. Rep., 14, 32175
  • L. Mazzei;* G. Tria; S. Ciurli; M. Cianci* “Exploring the conformational space of the mobile flap in Sporosarcina pasteurii urease by cryo-electron microscopy” 2024, Int. J. Biol. Macromol., 283, 137904
  • L. Rigobello, F. Lugli, L. Caporali, A. Bartocci, J. Fadanni, F. Zerbetto, L. Iommarini, V. Carelli, A.M. Ghelli and F. Musiani "A computational study to assess the pathogenicity of single or combinations of missense variants on respiratory Complex I" 2024, Int. J. Biol. Macromol., 273:133086
  • A. Pierro, K.C. Tamburrini, H. Leguenno, G. Gerbaud, E. Etienne, B. Guigliarelli, V. Belle, B.  Zambelli and E. Mileo "In cell investigation of the conformational landscape of the GTPase UreG by SDSL-EPR" 2023, iScience, 26:107855
  • B. Zambelli, P. Basak, H. Hu, M. Piccioli, F. Musiani, V. Broll, L. Imbert, J. Boisbouvier, M.J. Maroney and S. Ciurli "The structure of the high-affinity nickel-binding site in the Ni,Zn-HypA•UreE2 complex" 2023, Metallomics 15:mfad003

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