Viral and Microbial Proteins | Iva Pichová Group

About our group

The research of our laboratory focuses mainly on functional and structural studies of key proteins from Hepatitis B virus and Mycobacteria spp and their interactions with cellular proteins. We also study proteins from pathogenic yeasts and cooperate with chemical ecologists on insect pheromone biosynthetic enzymes.

Research projects involve protein engineering, protein purification, protein characterization, enzymology, NMR and X-ray protein structure solution, isolation and analysis of complexes of cellular and pathogenic proteins, various molecular biological methods, and electron microscopy analysis. Our close cooperation with organic chemists facilitates multidisciplinary research focused on identification and characterization of enzymes involved in drug metabolism and testing of potential inhibitors.

The group is a member of the project National Institute of Virology and Bacteriology of the Programme EXCELES.

The mycobacterial guaB1 gene encodes a guanosine 5′-monophosphate reductase with a cystathionine-β-synthase domain

Z. Knejzlík M. Doležal K. Herkommerová K. Clarová M. Klíma M. Dedola E. Zborníková D. Rejman I. Pichová

FEBS Journal 289 (18): 5571–5598 (2022)

Mycobacteria express enzymes from both the de novo and purine-salvage pathways. However, the regulation of these processes and the roles of individual metabolic enzymes have not been sufficiently detailed. Both Mycobacterium tuberculosis (Mtb) and Mycobacterium smegmatis (Msm) possess three guaB genes, but information is only available on guaB2, which encodes an essential inosine 5′-monophosphate dehydrogenase (IMPDH) involved in de novo purine biosynthesis. This study shows that guaB1, annotated in databases as a putative IMPDH, encodes a guanosine 5′-monophosphate reductase (GMPR), which recycles guanosine monophosphate to inosine monophosphate within the purine-salvage pathway and contains a cystathionine-β-synthase domain (CBS), which is essential for enzyme activity. GMPR activity is allosterically regulated by the ATP/GTP ratio in a pH-dependent manner. Bioinformatic analysis has indicated the presence of GMPRs containing CBS domains across the entire Actinobacteria phylum.

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Biogenesis of hepatitis B virus e antigen is driven by translocon-associated protein complex and regulated by conserved cysteine residues within its signal peptide sequence

H. Zábranská A. Zábranský B. Lubyová J. Hodek A. Křenková M. Hubálek J. Weber I. Pichová

FEBS Journal 289 (10): 2895–2914 (2022)

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Structural determinants for subnanomolar inhibition of the secreted aspartic protease Sapp1p from Candida parapsilosis

J. Dostál J. Brynda L. Vaňková S. R. Zia O. Heidingsfeld M. Lepšík

Journal of Enzyme Inhibition and Medicinal Chemistry 36 (1): 914-921 (2021)

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Understanding desaturation/hydroxylation activity of castor stearoyl Δ⁹-Desaturase through rational mutagenesis

M. Tupec M. Culka A. Machara S. Macháček D. Bím A. Svatoš L. Rulíšek I. Pichová

Computational and Structural Biotechnology Journal 20: 1378–1388 (2022)

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