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Our group is interested in the study of proteins involved in host-pathogen interactions and virulence processes, with a main interest in Mycobacterium tuberculosis, the causative agent of human Tuberculosis.


Our current research centers in the structural and functional characterization of cell-envelop protein factors playing key processes in M. tuberculosis’ virulence and life cycle. For this purpose, we use a multi-disciplinary approach combining Molecular Biology, Protein Engineering, and Structural Biology techniques. Our strategy implies the recombinant production of those protein factors and determining their three-dimensional structure using X-Ray Crystallography.

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Structural information is further complemented and validated using other molecular biology and biophysical studies. Altogether this enables us to obtain detailed information about how these macromolecules function at a molecular level and thus, to acquire a deep understanding of their biological function and role in pathogenesis. Moreover, our aim is using this knowledge to develop molecules with biotechnological interest, such new antimicrobials.

Publications

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New insights into the domain of unknown function DUF of EccC5, the pivotal ATPase providing the secretion driving force to the ESX5 secretion system

F. Ceballos-Zúñiga, M. Menéndez, I. Pérez-Dorado

To be published. Deposited in BioRxiv  (2004) (doi: 10.1101/2024.01.26.577026)

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PROTACs Targeting BRM (SMARCA2) Afford Selective In Vivo Degradation over BRG1 (SMARCA4) and Are Active in BRG1 Mutant Xenograft Tumor Models

M. Berlin, J. Cantley, M. Bookbinder, E. Bortolon, F. Broccatelli, G. Cadelina, E.W. Chan, H. Chen, X. Chen , Y. Cheng, T.K. Cheung, K. Davenport, D. DiNicola, D. Gordon, B.D. Hamman, A. Harbin, R. Haskell, M. He, A.J. Hole, T. Januario, P.S. Kerry, S.G. Koenig, L. Li, M. Merchant, I. Pérez-Dorado, J. Pizzano, C. Quinn, C.M. Rose, E. Rousseau, L. Soto, L.R. Staben, H. Sun, Q. Tian, J. Wang, W. Wang, C.S. Ye, X. Ye, P. Zhang, Y. Zhou, R. Yauch, P.S. Dragovich. 

Journal of Medicinal Chemistry (2024) 67, 1262-1313 (doi: 10.1021/acs.jmedchem.3c01781)

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Discovery of lipid-mediated protein–protein interactions in living cells using metabolic labeling with photoactivatable clickable probes.

R.O. Fedoryshchak, A. Gorelik, M. Shen, M.M. Shchepinova, I. Pérez-Dorado, and E.W. Tate

Chemical Science (2023) 14, 2419-2430 (doi: 10.1039/D2SC06116C)

 

Identification of the first structurally validated covalent ligands of the small GTPase RAB27A

M. Jamshidiha, T. Layon-Hogg, C.L. Sutherell, G.B. Craven, M. Tersa, E. De Vita, D. Brustur, I. Pérez-Dorado, S. Hassan, R. Petracca, R.M. Morgan, M. Sanz-Hermández, J.C. Norman, Al. Armstrong, D.J. Mann, E. Cota, and E.W. Tate.

RSC Medical Chemistry (2022) 13, 150-155 (doi: 10.1039/D1MD00225B)

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High-resolution snapshots of human N-myristoyltransferase in action illuminate a mechanism promoting N-terminal Lys and Gly myristoylation
C. Dian, I. Pérez-Dorado, F. Rivière, T. Asensio, P. Legrand, M. Ritzefeld, M. Shen, E. Cota, T. Meinnel, E.W. Tate, and C. Giglione
Nature Communications (2020) 28, 1132  (doi: 10.1038/s41467-020-14847-3)

Coping with strong translational noncrystallographic symmetry and extreme anisotropy in molecular replacement with Phaser: human Rab27a
M. Jamshidiha, I. Pérez-Dorado, J.W. Murray, E.W. Tate, E. Cota and R.J. Read
Acta Crystallographica (2019) D75, 342-353  (doi: 10.1107/S2059798318017825)

Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus
A. Mousnier, A.S. Bell, B.D. Swieboda, J. Morales-Sanfrutos, I. Pérez-Dorado, J.A. Brannigan, J. Newman, M. Ritzefeld, J.A. Hutton, A. Guedan, A.S. Asfor, S.W. Robinson, I. Hopkins-Navratilova, A.J. Wilkinson, S.L. Johnston, R.J. Leatherbarrow, T.J. Tuthill, R. Solari, and E.W. Tate
Nature Chemistry (2018) 10, 599-606  (doi: 10.1038/s41557-018-0039-2)

Unravelling the molecular basis of adhesion to the host via Als1, a major virulence factor from Candida albicans
I. Pérez-Dorado, S.M. Chee, L. Hale, R. Jones, N. Kichik, E. Tate, and E. Cota
FEBS Journal (2016) 283 (Suppl. 1), 78-78

Crystal structure of the CupB6 adhesive tip from the chaperone-usher family of pili from Pseudomonas aeruginosa
M. Rasheed, J. Garnett, I. Pérez-Dorado, D. Mulh, A. Filloux, S. Matthews 
Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics (2016) 1864, 1500-1505  (doi: 10.1016/j.bbapap.2016.07.010)

Structural insight into the TRIAP1-PRELI family of human mitochondrial phospholipid transfer complexes
X. Milara, J. Garnett, T. Tatsuta, F.A. Ali, H. Baldie, I. Pérez-Dorado, P. Simpson, E. Yague, T. Langer, and S. Matthews
EMBO Reports (2015) 16, 824-835  (doi: 10.15252/embr.201540229)

Structure and functions of choline binding proteins
S. Galán-Bartual, I. Pérez-Dorado, P. García and J.A. Hermoso
In Streptococcus Pneumoniae Molecular Mechanisms of Host-Pathogen Interactions (2015), Chap. 11, pp. 207-230. Jeremy Brown, Sven Hammerschmidt and Carlos Orihuela Eds., Elsevier. ISBN: 978-0-12-410530-0

VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell surface
G.G. Hesketh, I. Pérez-Dorado, L.P. Jackson, I.B. Schäffer, L. Wartosch, S.R. Gray, A.J. McCoy, O.B. Zeldin, E.F. Garman, M.E. Harbour, P.R. Evans, M.N.J. Seaman, J.P. Luzio, and D.J. Owen
Developmental Cell (2014) 9, 591-606   (doi: 10.1016/j.devcel.2014.04.010)

Structural and Phylogenetic Analysis of Rhodobacter capsulatus NifF: Uncovering General Features of Nitrogen-fixation (nif)-Flavodoxins
I. Pérez-Dorado and A. Bortolotti, N. Cortez, and J.A. Hermoso
International Journal of Molecular Sciences (2013) 14, 1152-1163  (doi:10.3390/ijms14011152)

Pneumococcal surface proteins: when the whole is greater than the sum of its parts
I. Pérez-Dorado, S. Galán-Bartual and J.A. Hermoso
Molecular Oral Microbiology (2012) 27, 221–245  (invited review) (doi:10.1111/j.2041-1014.2012.00655.x)

Insights into pneumococcal fratricide from crystal structure of the modular Killing Factor LytC
I. Pérez-Dorado, A. González, M. Morales, R. Sanles, W. Striker, W. Vollmer, S. Mobashery, J.L. García, M. Martínez-Ripoll, P. García and J.A. Hermoso
Nature Structural & Molecular Biology (2010) 17, 576-582 (doi:10.1038/nsmb.1817)

Crystallization of the pneumococcal autolysin LytC: in-house phasing using novel lanthanide complexes
I. Pérez-Dorado, R. Sanles, A. González, P. García, J.L. García, M. Martínez-Ripoll and J.A. Hermoso
Acta Crystallographica (2010) F66, 448-451 (doi:10.1107/S1744309110006081)

Structure and role in pathogenesis of pneumococcal cell-wall associated proteins
J.A. Hermoso, I. Pérez-Dorado and M. Martínez-Ripoll
Acta Crystallographica (2010) A66, s32-s32  (doi: 10.1107/S0108767310099290)

Discovery of specific flavodoxin inhibitors as potential therapeutic agents against Helicobacter pylori infection
N. Cremades, A. Velázquez-Campoy, M. Martínez-Júlvez, J.L. Neira, I. Pérez-Dorado, J.A. Hermoso, P. Jiménez, A. Lanas, P.S. Hoffman and J. Sancho
ACS Chemical Biology (2009) 4, 928-938  (doi: 10.1021/cb900166q)

Crystal structure of CbpF, a bifunctional choline-binding protein and autolysis regulator from Streptococcus pneumoniae
R. Molina, A, González, M. Stelter, I. Pérez-Dorado, R. Kahn, M. Morales, S. Campuzano, N.E. Campillo, S. Mobashery, J.L. García, P. García and J.A. Hermoso
EMBO Reports (2009) 10, 246-251  (doi: 10.1038/embor.2008.245)

Coenzyme binding and hydride transfer in Rhodobacter capsulatus ferredoxin/flavodoxin NADP(H) oxidoreductase
A. Bortoloti, I. Pérez-Dorado, G. Goñi, M. Medina, J.A. Hermoso, N, Carrillo and N. Cortez
Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics (2009) 1794, 199-210  (doi: 10.1016/j.bbapap.2008.09.013)

The coenzyme binding site of bacterial ferredoxin/flavodoxin-NADP(H) reductases
I. Pérez-Dorado, J.A. Hermoso, G. Goñi, M. Medina, A. Bortolotti, N. Carrillo, and N. Cortez
In Flavins and Flavoproteins (2008). S. Frago, C. Gómez-Moreno and M. Medina Eds. 267-273.  ISBN: 978-84-7733-017-2

Structural Characterization of the Ferredoxin:NADP(H) Reductase and a Flavodoxin from Rhodobacter capsulatus by X-ray Crystallography.
I. Pérez-Dorado, J.A. Hermoso, A. Bortolotti and N. Cortez
In Flavins and Flavoproteins (2008). S. Frago, C. Gómez-Moreno and M. Medina Eds.  pp.261-266. ISBN: 978-84-7733-017-2

Crystallization of a flavodoxin involved in the nitrogen fixation in Rhodobacter capsulatus
I. Pérez-Dorado, A. Bortolotti, N. Cortez and J.A. Hermoso
Acta Crystallographica (2008) F64, 375-377  (doi: 10.1107/S1744309108008038)

Tuning of the FMN binding and oxido-reduction properties by neighboring side chains in Anabaena Flavodoxin
S. Frago, G. Goñi, B. Herguedas, J.R. Peregrina, A. Serrano, I. Pérez-Dorado, R. Molina, C. Gómez-Moreno, J.A. Hermoso, M. Martínez-Júlvez, S. G. Mayhew and M. Medina
Archives of Biochemistry and Biophysics (2007) 467, 206-217  (doi:10.1016/j.abb.2007.08.024)

Elucidation of the Molecular Recognition of Bacterial Cell Wall by Modular Pneumococcal Phage Endolysin Cpl-1
I. Pérez-Dorado, N. E. Campillo, B. Monterroso, D. Hesek, M. Lee, J. A. Páez, P. García, M. Martínez-Ripoll, J. L. García, S. Mobashery, M. Menéndez and J.A. Hermoso
Journal of Biological Chemistry (2007) 282, 24990-24999  (doi:10.1074/jbc.M704317200

Common conformational changes in flavodoxins induced by FMN and anion binding: The structure of Helicobacter pylori apoflavodoxin
M. Martínez-Júlvez, N. Cremades, M. Bueno, I. Pérez-Dorado, C. Maya, S. Cuesta-López, D. Prada, F. Falo, J.A. Hermoso and. J. Sancho
Proteins: Structure, Function and Bioinformatics (2007) 69, 581-594  (doi:10.1002/prot.21410)

C-terminal Tyrosine of Ferredoxin-NADP+ reductase in the hydride transfer processes with NAD(P)+/H
J. Tejero, I. Pérez-Dorado, C. Maya, M. Martínez-Júlvez, J. Sanz-Aparicio, C. Gómez-Moreno, J.A. Hermoso and M. Medina
Biochemistry (2005) 44, 13477-13490  (doi:10.1021/bi051278c

The Ferredoxin-NADP(H) Reductase from Rhodobacter capsulatus: Molecular Structure and Catalytic Mechanism
I. Nogués, I. Pérez-Dorado, S. Frago, C. Bittel, S. G. Mayhew, C. Gómez-Moreno, J. A. Hermoso, M. Medina, N. Cortez, and N. Carrillo
Biochemistry (2005) 44, 11730-11740  (doi:10.1021/bi0508183)

Structural Analysis of Interactions for Complex Formation between Ferredoxin-NADP+ Reductase and Its Protein Partners
T. Mayoral, M. Martinez-Julvez, I. Pérez-Dorado, J. Sanz-Aparicio, C. Gomez-Moreno, M. Medina, and J.A. Hermoso
Proteins: Structure, Function, and Bioinformatics (2005) 59, 592-602  (doi:10.1002/prot.20450)

Crystallization and preliminary X-ray diffraction analysis of ferredoxin-NADP(H) reductase from Rhodobacter capsulatus
I. Pérez-Dorado. C. Bittel, N. Cortez and J.A. Hermoso
Acta Crystallographica (2004) D60, 2332-2335  (doi:10.1107/S090744490402640X)

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