C U R R I C U L U M V I T A E

INFORMAZIONI PERSONALI

Nome, Cognome

Indirizzo

Telefono

Fax

E-mail

Nazionalità

Data di Nascita

ESPERIENZA LAVORATIVA

ATTUALE

Stefano Mangani

Dipartimento Di Biotecnologie, Chimica e Farmacia dell’università Degli

Studi Di Siena, Via A. Moro N. 2, 53100, Siena, Italia

+39-0577-234255

+39-0577-234234

stefano.mangani@unisi.it

Italiana

26/06/1951

Dal 01/11/1997 alla sottoscrizione del presente documento

Università degli Studi di Siena, Via Banchi di Sotto, 55, 53100 - Siena

Dipartimento di Biotecnologie, Chimica e Farmacia, Via A. Moro n. 2, 53100 – Siena

Professore Ordinario di Chimica Generale ed Inorganica, Settore Scientifico Disciplinare CHIM/03 – Settore Concorsuale 03/B1 Fondamenti delle Scienze Chimiche e Sistemi Inorganici

Attività di Ricerca e di Didattica in ambito Universitario

Attività di Ricerca

Attività di Ricerca nell’ambito della Chimica Bioinorganica, della Cristallografia di composti di coordinazione e cristallografia di proteine, della spettroscopia di assorbimento di raggi-X applicata a sistemi bioinorganici (BioXAS), dello studio di meccanismi enzimatici e di sviluppo di farmaci.(Allegato 1).

Autore di più di 200 pubblicazioni fra articoli su riviste internazionali peer rewieved, riviste scientifiche nazionali e capitoli di libro di serie editoriali scientifiche (Allegato 2).

Autore, co-autore di oltre 220 strutture cristallografiche di proteine depositate nel Protein Data Bank e di 27 strutture di molecole depositate nel Cambridge Crystallographic Database.

Author metrics (Scopus - May 2020): H-index = 40. Total citations = 4891.

E’ stato invitato a numerosi convegni sia nazionali che internazionali come oratore ufficiale ed ha contribuito all’organizzazione di convegni, workshops e scuole nell’ambito della Chimica macromolecolare e nella Cristallografia e Strutturistica Chimica (Allegato 2).

Attività Didattica

Ha svolto continuativamente dal 1983 attività didattica frontale e di laboratorio per i Corsi di Laurea in Biologia, Chimica, Scienze Chimiche e per il corso di laurea Magistrale in “Chemistry” e Farmacia con corsi compresi nell’SSD CHIM/03 (Chimica Generale ed Esercitazioni, Chimica e Laboratorio di Chimica, Chimica Inorganica 2 e 3, Advanced Inorganic Chemistry, Protein Crystallography, Metodologia Avanzate di Processi Redox).

.

Ha svolto attività didattica anche in corsi di Dottorato in Scienze Chimiche e Farmaceutiche dell’Università di Siena e per l’International Doctorate in Structural Biology dell’Università di Firenze. Inoltre è stato docente di Scuole Internazionali organizzate da EMBO e docente ed organizzatore di Scuole nazionali organizzate dalla Divisione di Chimica Inorganica della Società Chimica Italiana Membro del Collegio dei Docenti del Dottorato in Chimica e poi in Scienze Chimiche e Farmaceutiche dell’Università di Siena. Dal 2013 al 2019 è stato Coordinatore del Dottorato in Chemical and Pharmaceutical Sciences dell’Università di Siena.

E’ Relatore di numerose Tesi di Laurea con argomenti di Chimica Bioinorganica e Cristallografia di proteine per le lauree triennali, specialistiche,e magistrali. Tutore di tesi di Dottorato di Ricerca in Scienze Chimiche e Farmaceutiche anche di di progetti ITN Marie-Curie.

Docente nelle Scuole estive per studenti della Emory University (Atlanta, Georgia – USA) tenuti nell’Università di Siena a partire dall’anno 2004.

Altre Attività

Dalla sua fondazione (anno 1994) è stato membro del Consiglio Direttivo del Consorzio Interuniversitario per la Ricerca su Metalloproteine Paramagnetiche con sede presso L’Università di Firenze.

Membro dell’International Advisory Board dell European Molecular Biology Laboratory (EMBL)

Membro dello Scientific Advisory Committee for XAS spectroscopy dell’ EMBL - Hamburg outstation.

Membro dello Scientific Advisory Committee for X-ray Crystallography at the European Synchrotron Radiation Facility (ESRF - Grenoble).

Membro dello Scientific Advisory Committee for XAS spectroscopy at the European Synchrotron Radiation Facility (ESRF - Grenoble).

Membro dello Scientific Advisory Committee for XAS spectroscopy of the Stanford Synchrotron Radiation Laboratory.

Membro dello Steering Group for X-ray Absorption Spectroscopy for Biology in Europe.

Revisore esterno per il CIVR Comitato Italiano per la Valutazione della Ricerca.

Membro della Società Chimica Italiana, dell’Associazione Italiana di Cristallografia. E’ anche nel Comitato Direttivo della Divisione di Chimica dei Sistemi Biologici della Società Chimica Italiana (dal 2017) e nel Comitato Direttivo della Sezione di Macromolecole Biologiche dell’Associazione Italiana di Cristallografia (dal 2017).

E’ membro dell’European Crystallographic Association, dell’American Crystallographic Association e della Society for Biological Inorganic Chemistry.

Svolga attività di revisore per le seguenti riviste scientifiche:

Proceedings of the National Academy of Sciences USA, Journal of the American Chemical

Society, Accounts of Chemical Research, Nature Microbiology, Biochemistry, Coordination

Chemistry Reviews, Inorganic Chemistry, Chemical Communications, PROTEINS:

Structure, Function, and Bioinformatics, FEBS Letters, FEMS, Biopolymers, Antimicrobial

Agents & Chemotherapy Inorganica Chimica Acta, European Journal of Inorganic

Chemistry, Journal of Inorganic Biochemistry, Journal of Biological Inorganic Chemistry,

Journal of Molecular Biology, Acta Crystallographica D and F, Journal of Synchrotron

Radiation, Structure, PlosOne. Crystal Growth & Design, Journal of Antimicrobial

Chemotherapy, Biomolecules, Bioinformatics, Journal of Molecular Catalysis B: Enzymatic,

Future Medicinal Chemistry, Journal Computer Aided Molecular Design, RSC Chemical

Sciences, Scientific Reports, ACS Medicinal Chemistry.

E’ membro del Comitato Editoriale per la rivista Molecules.

ESPERIENZE LAVORATIVE

PASSATE

PERIODI TRASCORSI

ALL’ESTERO

ISTRUZIONE E FORMAZIONE

CAPACITÀ E COMPETENZE

PERSONALI

MADRELINGUA

ALTRE LINGUE

Dal 01/11/1994 al 01/11/1997 Professore Straordinario di Chimica Generale ed Inorganica, Università di Siena.

Dal 16/05/1983 al 01/11/1994 Ricercatore Universitario di Chimica Generale ed Inorganica, Università di Siena.

Dal 16/02/1981 al 13/5/1983 Product Manager, Boehringer Ingelheim, Italia.

Dal 01/10/1979 al 20/12/1981 Postdoctoral Fellow presso il laboratorio del Prof. Edgar Meyer Jr. Department of Biochemistry and Biophysics – Texax A&M University – College Station TX- USA.

Dal 28/11/1978 al 09/09/1979 Docente di Chimica Industriale e Impianti Chimici –ITIS “G. Ferraris” Empoli (FI).

Dal 20/04/1977 al 12/04/1978 Servizio Militare.

Gennaio 1979 – Dicembre 1981 Postdoctorate studies at Texas A&M University –

College Station TX – USA

Estate 1983: visiting scientist in XAS spectroscopy in the EMBL-outstation in

Hamburg and in the University of Kiel c/o Prof. R. Haensel

Estate 1984 – 2016, visite periodiche EMBL outstation in Hamburg per

spettroscopia XAS e cristallografia di protein..

Autunno 1989: visiting scientist in protein crystallography in Prof. D.W.

Christianson laboratory, Department of Chemistry, University of Pennsylvania,

Philadelphia USA

Estate 1992: visiting scientist in protein crystallography in Prof. A. Liljas

laboratory, Department of Chemistry, University of Lund, Lund Sweden.

Estate 1994: visiting scientist in protein crystallography in Prof. R. Huber

laboratory, Max-Planck Institut für Biochemie, Martinsried, Germany

1998-ad oggi: periodic visits to ESRF – Grenoble, EMBL-Hamburg, Elettra -

Trieste for protein crystallography and X-ray absorption spectroscopy

Anno Accademico 1975-1976: Laurea in Chimica – Università di Firenze

Votazione: 110/110 e Lode.

Titolo della Tesi di Laurea: “Sonde Paramagnetiche nello Studio di Sistemi

Ternari in Biologia”

Relatore: Prof. Enzo Tiezzi Correltore Prof. Enzo Ferroni

Italiano

Inglese

CAPACITÀ DI LETTURA

CAPACITÀ DI SCRITTURA

CAPACITÀ DI ESPRESSIONE

ORALE

ALTRE LINGUE

CAPACITÀ DI LETTURA

CAPACITÀ DI SCRITTURA

CAPACITÀ DI ESPRESSIONE

ORALE

ESPERIENZE E COMPETENZE

TECNICHE

CAPACITÀ ORGANIZZATIVE

ALLEGATI

Ottima

Ottima

Ottima

Francese

Ottima

Buona

Buona

Vasta e riconosciuta esperienza e conoscenza delle tecniche e delle

strumentazioni cristallografiche (diffrazione di raggi-X da cristallo singolo, polveri,

uso di sorgenti di laboratorio e di luce di sincrotrone).

Vasta e riconosciuta esperienza di spettroscopia di assorbimento di raggi-X.

Padronanza di tecniche di sintesi inorganica, di cristallizzazione, di spettroscopie

UV-vis, CD, EPR, NMR

Conoscenze di sistemi operativi (Linux, Windows), di linguaggi di

programmazione (Fortran VII) e programmi di analisi di dati cristallografici e

spettroscopici.

Capacità di analisi e sintesi dei dati e dei risultati riportati nella letteratura

scientifica.

Esperienza pluriennale nell’organizazzione e direzione della ricerca, maturata

nell’ambito di numerosi progetti di ricerca finanziati da agenzie nazionali ed

internazionali (Allegato 3).

Organizzazione di Congressi scientifici (Allegato 2)

Allegato n. 1: Attività Scientifica

Allegato n. 2: Selezione delle pubblicazioni scientifiche e delle partecipazioni a

Congresso

Allegato n. 3: Recenti progetti di ricerca finanziati

Ai sensi dell’art. 13 del D. Lgs. 196/2003, autorizzo il trattamento dei dati

personali contenuti nel presente curriculum vitae”

Siena, 26 Maggio 2020

Stefano Mangani

Allegato n. 1 al CV di Stefano Mangani

Sintesi dell’ Attività Scientifica (in inglese)

Main field of research: structural biology, enzyme mechanism and bioinorganic chemistry

Research Themes:

1) Study of the catalytic mechanism and of the inhibition of bacterial β-lactamase enzymes of all classes

β-lactamase enzymes are a major defense system of bacteria against antibiotics and represent a threat for human health

since that they confer resistance against β-lactam antibiotics. Understanding the chemical basis of β-lactam antibiotics

inactivation and how β-lactamases can be inhibited is the starting point for developing new drugs to treat infections by

resistant bacterial strains. The main tool for the study is the determination, by X-ray crystallography, of the tridimensional

structure of β-lactamases and of their complexes with molecules able to provide information about the catalytic pathway.

These studies have provided important contributions to the development of β-lactamase inhibitors now used in therapy

like Avibactam or in phase III development like Taniborbactam.

2) Title: Mechanistic studies on metalloenzyme and metalloprotein function and inhibition.

Proteins and enzymes containing metal cofactors play crucial roles in cellular metabolism. The peculiar chemistry of metal

ions is exploited to perform the most difficult chemical reactions. The information coming from crystal structure

determination of such proteins and from x-ray absorption spectroscopy coupled to NMR spectroscopy is used to explain

at the molecular/atomic level the properties of such systems adding basic knowledge in the perspective of biotechnological

applications.

Some subjects: Eukaryotic metallothionein, eukaryotic ferritin, mammalian superoxide dismutase, human

carboxypeptidase, human carbonic anhydrase, bacterial dioxygenases, bacterial urease,

3) Title: Studies on inhibition and regulation of enzymes and proteins involved in cancer, neurodegenerative

disorders and neglected diseases.

These studies aim to provide the structural basis for the development of innovative drugs to fight different pathologies. The

understanding of protein function and the protein-protein interactions that are involved in metabolic pathways allows to

conceive innovative molecules able to regulate such pathways and to contrast the progression of such pathologies. The

systems studied are bacterial and human thymidylate sinthase; human Glutaminyl-peptide cyclotransferase (QPCT);

peptides involved in Alzheimer disease; pteridine reductase and dual dihydrofolate-thymidylate synthase from

Trypanosoma and Leishmania spp.

Allegato n. 2 al CV di Stefano Mangani

Selezione delle pubblicazioni e delle partecipazioni a Congresso

Scientific Publications:

Calderone V., Dolderer B., Hartmann H.J., Echner H., Luchinat C., Del Bianco C., Mangani S., Weser U. The Crystal Structure of Yeast Cu-Thionein: The Solution of a long lasting Enigma (2005) Proc. Natl. Acad. Sci. USA 102, 51-56. Banci L, Bertini I, Calderone V, Cramaro F, Del Conte R, Fantoni A, Mangani S, Quattrone A, Viezzoli MS A Prokaryotic SOD Paralog Lacking Two Cu Ligands: From largely Unstructured in Solution to Ordered in the Crystal (2005) Proc Natl Acad Sci U S A. 102(21), 7541-7546. Banci L, Benvenuti M, Bertini I, Cabelli DE, Calderone V, Fantoni A, Mangani S, Migliardi M, Viezzoli MS From an Inactive Prokaryotic SOD Homologue to an Active Protein through Site-Directed Mutagenesis (2005) J. Am. Chem. Soc. 127, 13287-13292.

Vito Calderone, Costantino Forleo, Manuela Benvenuti, Maria Cristina Thaller, Gian Maria Rossolini, Stefano Mangani A Structure Based Proposal for the Catalytic Mechanism of the Bacterial Acid Phosphatase AphA belonging to the DDDD Superfamily of Phosphohydrolases (2006) J. Mol. Biol. 355, 708-721. Claudio Passariello, Costantino Forleo, Vanna Micheli, Serena Schippa, Rosalida Leone, Stefano Mangani, Maria Cristina Thaller, and Gian Maria Rossolini Biochemical characterization of the class B acid phosphatase (AphA) of Escherichia coli (2006) Biochim. Biophys. Acta 64, 13-19. Calderone V, Casini A, Mangani S, Messori L, Orioli PL Structural Investigation of Cisplatin-Protein Interactions: Selective Platination of His19 in a Cuprozinc Superoxide Dismutase. (2006) Angew. Chem. Int. Ed. Engl. 45, 1267-1269. Arnesano F, Banci L, Bertini I, Capozzi F, Ciurli S, Luchinat C, Mangani S, Ciofi-Baffoni S, Rosato A, Turano P, Viezzoli MS An Italian Contribution to Structural Genomics: Understanding Metalloproteins. (2006) Coord. Chem. Rev. 250, 1419-1450. Lucia Banci, Ivano Bertini, Vito Calderone, Simone Ciofi-Baffoni, Stefano Mangani, Manuele Martinelli, Peep Palumaa, Shenlin Wang A hint for the function of human Sco1 from different structures. (2006) Proc Natl Acad Sci U S A. 103, 8595-8600. M. Benvenuti, S. Mangani Crystallisation of soluble proteins in vapour diffusion for x-ray crystallography. (2007) Nature Protocols, 2(7), 1633-1651. Daniela Martini, Maria Ranieri-Raggi, Antonietta R. M. Sabbatini, Arthur J.G. Moir, Enza Polizzi, Stefano Mangani, Antonio Raggi Characterization of the Metallocenter of Rabbit Skeletal Muscle AMP Deaminase. A new model for substrate interactions at a dinuclear cocatalytic Zn site. (2007) Biochimica et Biophysica Acta-Proteins and Proteomics; 1774(12):1508-1518. Leone R, Cappelletti E, Benvenuti M, Lentini G, Thaller MC, Mangani S. Structural insights into the catalytic mechanism of the bacterial class B phosphatase AphA belonging to the DDDD superfamily of phosphohydrolases. (2008) J Mol Biol. 384(2):478-88. Docquier JD, Calderone V, De Luca F, Benvenuti M, Giuliani F, Bellucci L, Tafi A, Nordmann P, Botta M, Rossolini GM, Mangani S. Crystal structure of the OXA-48 β-lactamase reveals mechanistic diversity among class D carbapenemases. (2009) Chem. Biol. 16(5):540-7. Agamennone M, Cesari L, Lalli D, Turlizzi E, Del Conte R, Turano P, Mangani S, Padova A. Fragmenting the S100B-p53 Interaction: Combined Virtual/Biophysical Screening Approaches to Identify Ligands. (2010) ChemMedChem. 13;5(3):428-435. Docquier JD, Benvenuti M, Calderone V, Giuliani F, Kapetis D, De Luca F, Rossolini GM, Mangani S Crystal Structure of the Narrow-Spectrum OXA-46 Class D β-lactamase: Relationship between Active Site Lysine Carbamylation and Inhibition by Polycarboxylates. .(2010) Antimicrob Agents Chemother. 54(5):2167-2174. Cardinale D, Salo-Ahen OM, Ferrari S, Ponterini G, Cruciani G, Carosati E, Tochowicz AM, Mangani S, Wade RC, Costi MP. Homodimeric Enzymes as Drug Targets.

(2010) Curr Med Chem. 17(9):826-846. Docquier JD, Benvenuti M, Calderone V, Stoczko M, Menciassi N, Rossolini GM, Mangani S. High-resolution crystal structure of the subclass B3 metallo-beta-lactamase BJP-1: rational basis for substrate specificity and interaction with sulfonamides. (2010) Antimicrob Agents Chemother. 54(10):4343-51. Stefano Mangani, Laura Cancian, Rosalida Leone, Cecilia Pozzi, Sandra Lazzari, Rosaria Luciani, Stefania Ferrari, M. Paola Costi Identification of N-phenylphthalimides as specific inhibitors of Bacterial Thymidylate Synthase through X-ray crystallography screening. (2011) J. Med. Chem. 54(15):5454-5467. Cardinale D, Guaitoli G, Tondi D, Luciani R, Henrich S, Salo-Ahen OM, Ferrari S, Marverti G, Guerrieri D, Ligabue A, Frassineti C, Pozzi C, Mangani S, Fessas D, Guerrini R, Ponterini G, Wade RC, Costi MP. Protein-protein interface-binding peptides inhibit the cancer therapy target human thymidylate synthase. (2011) Proc Natl Acad Sci U S A. 108(34):E542-549. De Luca F, Benvenuti M, Carboni F, Pozzi C, Rossolini GM, Mangani S, and Docquier JD Evolution to carbapenem -hydrolyzing activity in noncarbapenemase class D β-lactamase OXA-10 by rational protein design. (2011) Proc. Natl. Acad. Sci Usa 108, 18424-18429. Ivano Bertini, Daniela Lalli, Stefano Mangani, Cecilia Pozzi, Camilla Rosa, Elizabeth C. Theil, and Paola Turano Structural Insights into the Ferroxidase Site of Ferritins from Higher Eukaryotes (2012) J. Am. Chem. Soc. 134, 6169-6176. Lahiri SD, Mangani S, Durand-Reville T, Benvenuti M, De Luca F, Sanyal G, Docquier JD. Structural Insight into Potent Broad-Spectrum Inhibition with Reversible Recyclization Mechanism: Avibactam in Complex with CTX-M-15 and Pseudomonas aeruginosa AmpC β-Lactamases. Antimicrob Agents Chemother. (2013) 57(6):2496-2505. Stefano Mangani Protein–Protein Interactions in the Solid State: The Troubles of Crystallizing Protein–Protein Complexes. Chapt 5, pp 113-134 in Disruption of Protein-Protein Interfaces, S. Mangani Ed. 2013 Springer Berlin-Heidelberg DOI 10.1007/978-3-642-37999-4_5 Ferrari S, Calò S, Leone R, Luciani R, Costantino L, Sammak S, Di Pisa F, Pozzi C, Mangani S, Costi MP. 2'-Deoxyuridine 5'-Monophosphate Substrate Displacement in Thymidylate Synthase through 6-Hydroxy-2H-naphtho[1,8-bc]furan-2-one Derivatives. J Med Chem. (2013) 56(22), 9356-9360. Lahiri SD, Mangani S, Jahić H, Benvenuti M, Durand-Reville TF, De Luca F, Ehmann DE, Rossolini GM, Alm RA, Docquier JD. Molecular Basis of Selective Inhibition and Slow Reversibility of Avibactam against Class D Carbapenemases: A Structure-Guided Study of OXA-24 and OXA-48. ACS Chem Biol. (2015) 10(2), 591-600. De Ricco R, Valensin D, Dell'Acqua S, Casella L, Gaggelli E, Valensin G, Bubacco L, Mangani S. Differences in the Binding of Copper(I) to α- and β-Synuclein. Inorg Chem. (2015) 54(1):265-272. Salo-Ahen OM, Tochowicz A, Pozzi C, Cardinale D, Ferrari S, Boum Y, Mangani S, Stroud RM, Saxena P, Myllykallio H, Costi MP, Ponterini G, Wade RC.

Hotspots in an obligate homodimeric anti-cancer target. Structural and functional effects of interfacial mutations in human thymidylate synthase. J. Med. Chem. (2015) 58, 3572-3581. Cecilia Pozzi, Flavio Di Pisa, Daniela Lalli, Camilla Rosa, Elizabeth Theil, Paola Turano and Stefano Mangani Time-lapse anomalous X-ray diffraction shows how Fe2+ substrate ions move through ferritin protein nanocages to oxidoreductase sites. Acta Crystallogr D Biol Crystallogr. (2015) 71, 941–953. Docquier JD, Mangani S. Structure-Function Relationships of Class D Carbapenemases. Curr Drug Targets (2015) 17(9), 1061-1071. Cecilia Pozzi, Flavio Di Pisa, Caterina Bernacchioni, Silvia Ciambellotti, Paola Turano and Stefano Mangani Iron binding to human heavy-chain ferritin. Acta Crystallogr D Biol Crystallogr. (2015) Sep 1;71(Pt 9):1909-1920. Gardini S. et al. On Nature's Strategy for Assigning Genetic Code Multiplicity. PlosOne (2016) 11(2):e0148174. Borsari C, Luciani R, Pozzi C, Poehner I, Henrich S, Trande M, Cordeiro-da-Silva A, Santarem N, Baptista C, Tait A, Di Pisa F, Dello Iacono L, Landi G, Gul S, Wolf M, Kuzikov M, Ellinger B, Reinshagen J, Witt G, Gribbon P, Kohler M, Keminer O, Behrens B, Costantino L, Tejera Nevado P, Bifeld E, Eick J, Clos J, Torrado J, Jiménez-Antón MD, Corral MJ, Alunda JM, Pellati F, Wade RC, Ferrari S, Mangani S, Costi MP. Profiling of Flavonol Derivatives for the Development of Antitrypanosomatidic Drugs. J Med Chem. 2016 59(16):7598-7616. doi: 10.1021/acs.jmedchem.6b00698. Catalano A, Luciani R, Carocci A, Cortesi D, Pozzi C, Borsari C, Ferrari S, Mangani S. X-ray crystal structures of Enterococcus faecalis thymidylate synthase with folate binding site inhibitors. Eur J Med Chem. (2016) 123:649-664. doi: 10.1016/j.ejmech.2016.07.066. Pozzi C, De Luca F, Benvenuti M, Poirel L, Nordmann P, Rossolini GM, Mangani S, Docquier JD. Crystal Structure of the Pseudomonas aeruginosa BEL-1 Extended-Spectrum β-Lactamase and Its Complexes with Moxalactam and Imipenem. Antimicrob Agents Chemother. (2016) 60(12):7189-7199. Pozzi C, Ciambellotti S, Bernacchioni C, Di Pisa F, Mangani S, Turano P. Chemistry at the protein-mineral interface in L-ferritin assists the assembly of a functional (μ3-oxo)Tris[(μ2-peroxo)] triiron(III) cluster. Proc Natl Acad Sci U S A. (2017) 114(10):2580-2585. doi: 10.1073/pnas.1614302114. Linciano P, Dawson A, Pöhner I, Costa DM, Sá MS, Cordeiro-da-Silva A, Luciani R, Gul S, Witt G, Ellinger B, Kuzikov M, Gribbon P, Reinshagen J, Wolf M, Behrens B, Hannaert V, Michels PAM, Nerini E, Pozzi C, di Pisa F, Landi G, Santarem N, Ferrari S, Saxena P, Lazzari S, Cannazza G, Freitas-Junior LH, Moraes CB, Pascoalino BS, Alcântara LM, Bertolacini CP, Fontana V, Wittig U, Müller W, Wade RC, Hunter WN, Mangani S, Costantino L, Costi MP. Exploiting the 2-Amino-1,3,4-thiadiazole Scaffold To Inhibit Trypanosoma brucei Pteridine Reductase in Support of Early-Stage Drug Discovery. ACS Omega. (2017) 2(9):5666-5683. doi: 10.1021/acsomega.7b00473. Docquier JD, Mangani S. An update on β-lactamase inhibitor discovery and development. Drug Resist Updat. (2018) 36:13-29. doi: 10.1016/j.drup.2017.11.002.

Leiris S, Coelho A, Castandet J, Bayet M, Lozano C, Bougnon J, Bousquet J, Everett MJ, Lemonnier M, Sprynski N, Zalacain M, Pallin TD, Cramp M, Jennings N, Raphy G, Jones MW, Pattipati R, Shankar B, Sivasubrahmanyam R, Soodhagani AK, Juventhala RR, Pottabathini N, Pothukanuri S, Benvenuti M, Pozzi C, Mangani S, De Luca F, Cerboni G, Docquier JD, Davies D. SAR studies leading to the identification of a novel series of metallo-β-lactamase inhibitors for the treatment of carbapenem-resistant Enterobacteriaceae infections that display efficacy in an animal infection model. ACS Infect Dis. (2019) 5(1):131-140. doi: 10.1021/acsinfecdis.8b00246. Landi G, Linciano P, Borsari C, Bertolacini CP, Moraes CB, Cordeiro-da-Silva A, Gul S, Witt G, Kuzikov M, Costi MP, Pozzi C, Mangani S. Structural Insights into the Development of Cycloguanil Derivatives as Trypanosoma brucei Pteridine-Reductase-1 Inhibitors. ACS Infect Dis. (2019) 5(7), 1105-1114. doi: 10.1021/acsinfecdis.8b00358. Pozzi C, Di Pisa F, Lalli D, Rosa C, Turano P, Mangani S. Effect of the point mutation H54N on the ferroxidase process of Rana catesbeiana H' ferritin. J Inorg Biochem. (2019) 197:110697. doi: 10.1016/j.jinorgbio.2019.110697. Bloch DN, Kolkowska P, Tessari I, Baratto MC, Sinicropi A, Bubacco L, Mangani S, Pozzi C, Valensin D, Miller Y. Fibrils of α-Synuclein Abolish the Affinity of Cu2+-Binding Site to His50 and Induce Hopping of Cu2+ Ions in the Termini. Inorg Chem. (2019) 58(16):10920-10927. doi: 10.1021/acs.inorgchem.9b01337. Leiris, S., Coelho, A., Castandet, J., Bayet, M., Lozano, C., Bougnon, J., Bousquet, J., Everett, M., Lemonnier, M., Sprynski, N., Zalacain, M., Pallin, T.D., Cramp, M.C., Jennings, N., Raphy, G., Jones, M.W., Pattipati, R., Shankar, B., Sivasubrahmanyam, R., Soodhagani, A.K., Juventhala, R.R., Pottabathini, N., Pothukanuri, S., Benvenuti, M., Pozzi, C., Mangani, S., De Luca, F., Cerboni, G., Docquier, J.-D., Davies, D.T. SAR Studies Leading to the Identification of a Novel Series of Metallo-β-lactamase Inhibitors for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections That Display Efficacy in an Animal Infection Model. ACS Inf. Diseases (2019) 5(1), 131-140. DOI: 10.1021/acsinfecdis.8b00246

Hamrick, J.C., Docquier, J.-D., Uehara, T., Myers, C.L., Six, D.A., Chatwin, C.L., John, K.J., Vernacchio, S.F., Cusick, S.M., Trout, R.E.L., Pozzi, C., De Luca, F., Benvenuti, M., Mangani, S., Liu, B., Jackson, R.W., Moeck, G., Xerri, L., Burns, C.J., Pevear, D.C., Daigle, D.M. VNRX-5133 (Taniborbactam), a broad-spectrum inhibitor of serine- And metallo-β-lactamases, restores activity of cefepime in enterobacterales and Pseudomonas aeruginosa. Antimicrobial Agents Chemotherapy. (2020) 64(3), e01963-19. doi: 10.1128/AAC.01963-19. Ciambellotti, S., Pozzi, C., Mangani, S., Turano, P. Iron Biomineral Growth from the Initial Nucleation Seed in L-Ferritin Chemistry - A European Journal (2020) 26(26), 5770-5773. doi: 10.1002/chem.202000064. Liu B, Trout REL, Chu GH, McGarry D, Jackson RW, Hamrick JC, Daigle DM, Cusick SM, Pozzi C, De Luca F, Benvenuti M, Mangani S, Docquier JD, Weiss WJ, Pevear DC, Xerri L, Burns CJ. Discovery of Taniborbactam (VNRX-5133): A Broad-Spectrum Serine- And Metallo-β-lactamase Inhibitor for Carbapenem-Resistant Bacterial Infections. J Med Chem.(2020) 63(6):2789-2801. doi: 10.1021/acs.jmedchem.9b01518. Selected Invited Congress Participations:

ICTP, ICGEB, SISSA Workshop on the Structure of Biological Macromolecules, Trieste, March 16-27, 1998.

Workshop on X-ray Absorption Spectroscopy for Biology Using a Third Generation Source, ESRF Grenoble,

February 15-16, 1999.

BioXas 2000, European Workshop on X-ray Absorption for Biology, LURE, Paris, July 2-4, 2000. EUROBIC 2000, European Bioinorganic Chemistry Conference, Toulouse, July 15-20, 2000.

International Conference on Synchrotron Radiation: Perspectives and new technologies. Accademia dei Lincei, Roma, May 8-9, 2001. Chair of the 3rd European Workshop on X-ray Absorption for Biology - BioXAS2001, Siena 2-4 September 2001. XXXII Congress of the Italian Crystallographic Association, Bressanone, September 24-27 2002. 7th FIGIPS Meeting in Inorganic Chemistry, Lisboa, June 11-14, 2003. 2nd BioXAS Study Weekend “Genomics and BioXAS”, Paris, June 29-30, 2003. American Crystallographic Association annual meeting, Chicago, July 17-22, 2004. National Congress of the Bioinorganic Division of the Italian Chemical Society, Siena, May 2005. Member of the Local Organizing Committee of the XX IUCr Congress, Firenze, 23-31 August 2005. 8th FIGIPAS Meeting in Inorganic Chemistry, Athens, July 6-9 2005. RAMC 2007 Recent Advances in Macromolecular Crystallization, San Diego CA, September 23-26, 2007. XXI Congress of the International Union of Crystallography, Osaka, Japan, August 23-31, 2008. XXIII congress of the Italian Chemical Society, Sorrento, Italy, 5-10 Luglio 2009. Member of the Organizing Committee of the 2nd International Workshop on Expression, Structure, Function of membrane Proteins, Firenze, September 20-24 2009. Chair of the Organizing Committee of the XL Congress of the Italian Crystallographic Association, 19-23 September 2011, Siena XLI Congresso AIC – Verona – 11-14 Settembre 2012 Member of the Organizing Committee of the 3rd International Workshop on Expression, Structure, Function of membrane Proteins, Firenze, September 23-27 2012. Member of the Organizing Committee of the 4th International Workshop on Expression, Structure, Function of membrane Proteins, Firenze, June 28 - July 2 2015. Società Chimica Italiana - Convegno Nazionale della Divisione della Chimica dei Sistemi Biologici, Siracusa, September 24-25 2015 New synchrotron radiation and optical techniques for nanoscale microscopy of biological systems: from single molecules to cells. Trieste, Dec 9-10 2015. Protein crystallography contribution to drug discovery platforms. Benefits and pitfalls. 3rd Joint AIC-SILS Conference – Rome, August 2018. Member of the Organizing Committee of the National Congress of the Chemistry of Biological Systems of the Italian Chemical Society. Caserta, September 2018. Head of the Organizing Committee of the National Congress of the Chemistry of Biological Systems of the Italian Chemical Society. Siena, September 2019.

Allegato n. 3 al CV di Stefano Mangani Recenti progetti scientifici finanziati Local coordinator for the Italian project PRIN2009 (Progetti di Ricerca Scientifica di Rilevante Interesse Nazionale) 2009FAKHZT_001 Title: Mechanistic structural biology: methodological and biological advances. The project is dedicated to new methodologies for the characterization of the structure, dynamics and intermolecular interactions of proteins. Scientific local coordinator of the FP6 European Project LIGHTS: Ligands to Interfere with Human Thymidylate Synthase dimer formation as new tools for development of anticancer agents against ovarian carcinoma. 2007-2010. This project aims to develop new molecules as interface inhibitors of human thymidylate enzyme able to stop proliferative activities of cancer cells and at the same time avoiding the drug resistance phenomena observed with conventional active-site directed inhibitors. Local coordinator for the Italian project PRIN2012 (Progetti di Ricerca di Rilevante Interesse Nazionale) 2012SK7ASN_001 . Title: Innovative chemical methodologiesto develop advanced molecular strategies in biomedicine. Scientific local coordinator for the European action POR Creo Fesr 2010-2013 FINDING Title: Innovative drugs for neurodegenerative pathologies.

The project aims to identify and optimize new chemicals for the development of a chronic therapy of Alzheimer disease.The goal of the project is to identify and optimize new chemical entities, inhibitors of the human enzyme glutaminyl cyclase (QPCT), to allow the development chronic therapies of Alzheimer disease, a syndrome for which there is no effective therapy and affecting more than 30 million people worldwide. PI of the University of Siena unit for the AIRC project: Targeting ovarian cancer drug resistance. Upon the discovery of new inhibition mechanism of thymidylate synthase, the project aims to develop new inhibitors of ovarian cancer cell growth. Ovarian cancer (OC) represents the fifth most common cause of death from cancer in women. The standard first-line treatment is a combination of paclitaxel and carboplatin (DDP). Drug resistance is commonly observed during therapy. Following the observation of a new inhibition mechanism of the enzyme thymidylate synthase involved in OC and subject of a FP6 European study participated by us, we conceived this new project aimed to develop molecules for the inhibition of OC cell growth avoiding resistance phenomena. Scientific coordinator of the University of Siena unit for the European project health FP7 2013-2017: NMTrypl Title: New medicines for trypanosomatidic infections The infectious diseases burden imposed by the parasites of Trypanosomatidae family represents a huge problem. The project uses a highly interdisciplinary approach to optimize drugs against Trypanosomatids. Iinfectious diseases burden imposed by the parasites of Trypanosomatidae family represents a huge problem on people’s lives in countries where diseases are endemic. Problems associated with existing drugs include inefficient delivery, insufficient efficacy, excessive toxicity and increasing resistance. New drugs are urgently needed. The project uses a highly interdisciplinary approach to optimize pteridine, benzothiazole and miltefosine derivatives as well as natural products against Trypanosomatids. PI of the University of Siena unit for the AIRC project: Protein-protein interaction inhibitors of thymidylate synthase against colorectal cancer (2015-2018). Thymidylate synthase (TS) plays a key role in cancer development and its inhibition is very effective in different types of cancer including NSLC (non-small cell lung cancer), colorectal cancer (CRC), mesothelioma, and, as recently studied, in ovarian cancer. More than 1600 clinical trials have been started over the latest 5 years (www.medtrack.com) using the following drugs: pemetrexed, raltitrexed, 5Fu, pralatrexate, and methotrexate. All the therapeutical drugs exhibit similar side effects and drug resistance development, involving in particular a number of folate related proteins, folate receptor transporters, and TS as key proteins. The problem posed is how to solve the drug resistance problems of such widely used drugs, and how to identify new TS targeting drugs, considering that TS-targeting is one of the widely used target-directed chemotherapeutical approaches in clinical treatment (targeted therapy). The discovery of new allosteric (non-TS active site) inhibitors would be extremely important. These novel approaches will be applied to a case of colon cancer in this study. Scientific coordinator of the University of Siena unit for the European project Horizon2020, Marie Sklodowska-Curie, MSCA-ITN-2017-ETN, 2018-2021 “EuroNeurotrophin: A European training network for the discovery of neurotrophins small molecule mimetics as candidate therapeutic agents for neurodegeneration and neuroinflammation.” The key idea behind this project is to address this limitation by developing novel small molecule, neurotrophin mimetics with favorable profiles of stability, tissue penetration and targeted biological actions.