Marco Mazzorana

profilephoto

Industrial Liaison Scientist - Macromolecular Crystallography

Email: industry@diamond.ac.uk
Tel: +44 (0) 1235 778643

Key Research Area

Key Research Area

 Structural Biology

Latest Publications

Please Wait
  1. Biography
  2. Responsibilities
  3. Research Interests
  4. Publications
Biography -

Biography

Marco Mazzorana graduated in Organic Chemistry at the University of Padua under the direction of Prof. Giuseppe Zanotti. He then joined the group of Professor Lorenzo A. Pinna for his Ph.D. in Biochemistry and Biophysics. His thesis focused on the structural characterisation of protein kinase CK2 isoforms and of protein-inhibitor complexes.
 
After a short post-doc at the Venetian Institute of Molecular Medicine (VIMM, Padua) and three years at the Spanish National Cancer Research Centre (CNIO, Madrid), he joined Diamond Light Source as part of the I02 Beamline team in March 2011.
 
Marco now joins the Industrial Liaison team as an Industrial Liaison Scientist - Macromolecular Crystallography
 
Responsibilities - +

Responsibilities

My role as an Industrial Liaison Scientist is to assist industrial users with diffraction data collection on the MX beamlines and further establish and maintain collaboration with Diamond’s industrial partners. Together with other members of the Industrial Liaison team I work towards gaining maximal benefit from accessibility of complementary techniques such as Small Angle X-ray Scattering (SAXS) or Circular Dichroism (CD) to provide complex information about biological systems.

Research Interests - +

Research Interests

Structural biology of membrane proteins

Membrane proteins are fundamental to cell life and regulation. A large number of transporters, signalling and metabolic proteins are anchored to or are completely embedded in biological membranes. It has been estimated that a third of the human genome encodes for membrane proteins and for this reason they represent a growing field of research in structural biology. MsbA, a member of the large family of ATP-binding cassette transporters (ABC), hydrolyses ATP to promote the translocation of lipid A through the inner membrane of Gram negative bacteria. This is a crucial step to the formation of biofilms protecting bacteria such as Pseudomonas aeruginosa from the attack of the immune system are composed of lipid A. For this reason, MsbA and similar ABC-transporters represents a promising target of antibiotics research. I use biochemical and biophysical techniques to achieve better insight in the structure/function relationships of paMsbA, with particular emphasis in the crystallographic aspect and toward the design of new antibiotics.

Human calcium binding proteins

Calcium is widely exploited in eukaryotic cells, especially to trigger specific responses to signalling events. The release of calcium from intracellular stores triggers a number of cellular events, usually mediated by proteins such Calmodulin, which undergo major structural rearrangements upon Ca-binding. The cross-talk among various forms of signalling, including extracellular receptors, phosphorylation and other second messengers, are crucial for the correct tuning of the calcium response to stimuli. Spatial and temporal control of calcium signalling is therefore fundamental for muscle contraction, neurotransmission, cell growth and motility. A detailed structural description of these proteins and complexes would let us better understand the regulation of calcium signalling within eukaryotic cells. I am studying a group of calcium-binding proteins and their interactions with some of their regulators. In particular I am interested in the Sarco-Endoplasmic reticulum P-type Ca-ATPase (SERCA) and some of its functional partners. I make use of CD, SAXS and X-ray crystallography to understand how the crosstalk among these proteins finely regulates the contraction of the cardiac muscle.

Protein kinases and phosphatases

Post-translational modifications tagging proteins are widely used as molecular switches. In humans a large number of kinases and phosphatases control pathways by catalysing the reversible phosphorylation of nucleophilic protein side chains. Deregulation of the complex phosphorylation network of a cell often results in pathologies such as metabolic and proliferative diseases. For this reason, protein kinases are considered a hot topic both from academia and from pharmaceutical companies. Currently I am helping to develop techniques for the biochemical characterisation of some members of this class of enzymes. I am also continuing to work with older collaborations, on the structural description of kinase-inhibitor complexes as well as on protein phosphatases and their physiological modulators

Crystal handling tools

Together with the staff of the MX beamline I02, I am also working on novel crystal handling tools for the improvement of room temperature and humidity-controlled x-ray diffraction experiments.

Publications - +

Publications

  1. Aller P, Sanchez-Weatherby J, Foadi J, Winter G, Lobley CM, Axford D, Ashton AW, Bellini D, Brandao-Neto J, Culurgioni S, Douangamath A, Duman R, Evans G, Fisher S, Flaig R, Hall DR, Lukacik P, Mazzorana M, McAuley KE, Mykhaylyk V, Owen RL, Paterson NG, Romano P, Sandy J, Sorensen T, von Delft F, Wagner A, Warren A, Williams M, Stuart DI, Walsh MA (2015) Application of in situ diffraction in high-throughput structure determination platforms. Methods Mol Biol. 1261:233-53.
  2. Mazzorana M, Sanchez-Weatherby J, Sandy J, Lobley CM, Sorensen T. An evaluation of adhesive sample holders for advanced crystallographic experiments. (2014) Acta Crystallogr D Biol Crystallogr. 2014 Sep;70(Pt 9):2390-400.
  3. Zonta F, Pagano MA, Trentin L, Tibaldi E, Frezzato F, Gattazzo C, Martini V, Trimarco V, Mazzorana M, Bordin L, Semenzato G, Brunati AM. (2014) Lyn-mediated procaspase 8 dimerization blocks apoptotic signaling in B-cell chronic lymphocytic leukemia. Blood. 2014 Feb 6;123(6):875-83
  4. Lolli G, Cozza G, Mazzorana M, Tibaldi E, Cesaro L, Donella-Deana A, Meggio F, Venerando A, Franchin C, Sarno S, Battistutta R, Pinna LA (2012) Inhibition of protein kinase CK2 by flavonoids and tyrphostins. A structural insight. Biochemistry, 51(31):6097-6107.
  5. Pastor J, Oyarzabal J, Saluste G, Alvarez RM, Rivero V, Ramos F, Cendón E, Blanco-Aparicio C, Ajenjo N, Cebriá A, Albarrán MI, Cebrián D, Corrionero A, Fominaya J, Montoya G, Mazzorana M (2012) Hit to lead evaluation of 1,2,3-triazolo[4,5-b]pyridines as PIM kinase inhibitors. Bioorg Med Chem Lett, 22(4):1591-1597.
  6. Sarno S, Mazzorana M, Traynor R, Ruzzene M, Cozza G, Pagano MA, Meggio F, Zagotto G, Battistutta R, Pinna LA (2012) Structural features underlying the selectivity of the kinase inhibitors NBC and dNBC: role of a nitro group that discriminates between CK2 and DYRK1A. Cell Mol Life Sci, 69(3):449-460.
  7. Mazzorana M, Montoya G, Mortuza GB (2011) The centrosome: a target for cancer therapy. Curr Cancer Drug Targets 2011, 11(5):600-612
  8. Bidoia C, Mazzorana M, Pagano MA, Arrigoni G, Meggio F, Pinna LA, Bertazzoni U (2010) The pleiotropic protein kinase CK2 phosphorylates HTLV-1 Tax protein in vitro, targeting its PDZ-binding motif. Virus Genes 2010, 41(2):149-157.
  9. Cozza G, Mazzorana M, Papinutto E, Bain J, Elliott M, di Maira G, Gianoncelli A, Pagano MA, Sarno S, Ruzzene M, Battistutta R, Meggio F, Moro S, Zagotto G, Pinna LA (2009) Quinalizarin as a potent, selective and cell-permeable inhibitor of protein kinase CK2. Biochem J, 421(3):387-395.
  10. Mazzorana M, Pinna LA, Battistutta R (2008) A structural insight into CK2 inhibition. Mol Cell Biochem, 316(1-2):57-62.
  11. Chilin A, Battistutta R, Bortolato A, Cozza G, Zanatta S, Poletto G, Mazzorana M, Zagotto G, Uriarte E, Guiotto A, Pinna LA, Meggio F, Moro S (2008) Coumarin as attractive casein kinase 2 (CK2) inhibitor scaffold: an integrate approach to elucidate the putative binding motif and explain structure-activity relationships. J Med Chem, 51(4):752-759.
  12. Battistutta R, Mazzorana M, Cendron L, Bortolato A, Sarno S, Kazimierczuk Z, Zanotti G, Moro S, Pinna LA (2007) The ATP-binding site of protein kinase CK2 holds a positive electrostatic area and conserved water molecules. Chembiochem, 8(15):1804-1809.
  13. Sarno S, Ruzzene M, Frascella P, Pagano MA, Meggio F, Zambon A, Mazzorana M, Di Maira G, Lucchini V, Pinna LA (2005) Development and exploitation of CK2 inhibitors. Mol Cell Biochem 274(1-2):69-76.
  14. Battistutta R, Mazzorana M, Sarno S, Kazimierczuk Z, Zanotti G, Pinna LA (2005) Inspecting the structure-activity relationship of protein kinase CK2 inhibitors derived from tetrabromo-benzimidazole. Chem Biol, 12(11):1211-1219.