Ita Gruic

dr. sc. Ita Gruić Sovulj

Professor

Contact
Room: 303/ZBK
Tel: +385 1 4606 230
Mail: gruic[at]chem.pmf.hr
Official Faculty page

Education
2001. PhD degree, thesis on “Noncovalent interactions of aminoacyl-tRNA synthetases : the influence of tRNA on SerRS affinity toward other substrates”, under mentorship of prof. dr. sc. Željko Kućan, Division of Biochemistry, Department of Chemistry, University of Zagreb

1998. Master degree, thesis on “Inhybition of tyrosyl-tRNA synthetase from Saccharomyces cerevisiae by modified tRNATyr under mentorship of prof. dr. sc. Željko Kućan, Division of Biochemistry, Department of Chemistry, University of Zagreb

1993. Diploma thesis in Chemistry

Research interests
Research in my group is concentrated on the mechanisms that ensure high level of specificity in protein translation. We investigate aminoacyl-tRNA synthetases (aaRS) and their specificity in recognition of the amino acid substrates in aminoacylation reaction. We also study the proofreading mechanisms employed by some aaRSs to ensure high level of specificity in aminoacyl-tRNA synthesis when initial enzyme discrimination against similar non-cognate amino acids is limiting. Recently, we became interested in non-canonical mistranslation and production of the proteins containing noncanonical amino acids. In our work we use standard biochemical and molecular biology methods, steady-state and transient enzyme kinetics, biophysical techniques (ITC, fluorescence) and some genetic approaches.

Research Projects - Project Leader

2019 - 2022
Investigation of substrate and editing specificity in tRNA synthetases and the mechanism of antibiotic action
Funding: Swiss National Science Foundation (SNSF) and the Croatian Science Foundation (CSF; HRZZ)
Principal investigators: Ita Gruić Sovulj and Nenad Ban

2018 - 2020
Cellular responses to canonical and non-canonical mistranslation
Funding: Ministry of Science and Education of the Republic of Croatia and DAAD (a bilateral Croatian-German project)
Principal investigators: Ita Gruić Sovulj and Boris Maček

2017 - 2021
Aminoacyl-tRNA synthetases as gatekeepers of the standard genetic code
Funding: Croatian Science Foundation
Principal investigator: Ita Gruić Sovulj

2014 - 2016
Role of translational quality control mechanisms in maintaining the functional Escherichia coli proteome
Funding: Ministry of Science, Education and Sport of the Republic of Croatia and DAAD (a bilateral Croatian-German project)
Principal investigators: Ita Gruić Sovulj and Boris Maček

2013 - 2016
Non-canonical roles of aminoacyl-tRNA synthetases
Funding: Croatian Science Foundation
Principal investigators: Ivana Weygand-Đurašević and Ita Gruić Sovulj

2013 - 2016
Integrating research in molecular life sciences at the University of Zagreb - INTEGRA-LIFE (EU FP7); work package 4
Funding: INTEGRA-LIFE (EU FP7); work package 4
Principal investigators: Ivana Weygand-Đurašević and Ita Gruić Sovulj

2013 - 2015
The origin of amino acid specificity in editing class I aminoacyl-tRNA synthetases and cellular requirements for proofreading
Funding: Unity Through Knowledge Fund
Principal investigators: Ita Gruić Sovulj
Co-Principal Investigator: Boris Lenhard

2013 - 2015
Mapping of the isoleucyl-tRNA synthetase active site aimed to develop new inhibitors
Funding: ADRIS Foundation
Principal investigator: Ita Gruić Sovulj

2008 - 2011
Mechanism of proofreading by class I aminoacyl-tRNA synthetases
Funding: NIH/FIRCA (R03 TW008024-01A1)
Principal investigators: John J. Perona and Ita Gruić Sovulj

Research Projects - Project Participant

2007 - 2013
Structural diversity of seryl-tRNA synthetases and accuracy of protein synthesis
Funding: Ministry of Science, Education and Sports of the Republic of Croatia

2007 - 2010
Macromolecular complexes of aminoacyl-tRNA synthetases and their role in translational quality control and non-ribosomal peptide synthesis
Funding: Unity Through Knowledge Fund

2005 - 2008
Structural studies of atypical seryl-tRNA synthetases from methanogenic archaea (continuation)
Funding: Scientific Co-operation between Eastern Europe and Switzerland

2002 - 2007
Quality control mechanisms in seryl-tRNA biosynthesis
Funding: Ministry of Science, Education and Sports of the Republic of Croatia

2001 - 2003
X-ray crystallographic and biochemical studies of unusual archaeal seryl-tRNA synthetases
Funding: Scientific Co-operation between Eastern Europe and Switzerland

1996 - 2002
Structure, function and evolution of aminoacyl-tRNA synthetases
Funding: Ministry of Science, Education and Sports of the Republic of Croatia

1995 - 1998
Natural and recombinant tRNA synthetases: studies on structure and function
Funding: Bilateral Cooperation in Scientific Research and Technological Development between Croatia and FR Germany

1991 - 1996
Aminoacyl-tRNA synthetases: gene structure and protein function
Funding: Ministry of Science, Education and Sports of the Republic of Croatia

Publications
The evolutionary history of the HUP domain.
Critical Reviews in Biochemistry and Molecular Biology (2021), doi:10.1080/10409238.2021.1957764
Ita Gruic-Sovulj, Liam M. Longo, Jagoda Jablonska, Dan S. Tawfik

Polyamines Mediate Folding of Primordial Hyperacidic Helical Proteins.
Biochemistry. 59 (2020), 4456-4462, doi:10.1021/acs.biochem.0c00800
Dragana Despotović, Liam M. Longo, Einav Aharon, Amit Kahana, Tali Scherf, Ita Gruic-Sovulj, Dan S. Tawfik

How evolution shapes enzyme selectivity – lessons from aminoacyl‐tRNA synthetases and other amino acid utilizing enzymes.
The FEBS Journal. 287 (2020), 1284-1305, doi:10.1111/febs.15199
Dan S. Tawfik; Ita Gruic-Sovulj

Mechanism of discrimination of isoleucyl‐tRNA synthetase against non‐proteinogenic α‐amino butyrate and its fluorinated analogues
The FEBS Journal. 2020, doi:/10.1111/febs.15053
Igor Zivkovic; Johann Moschner; Beate Koksch; Ita Gruic Sovulj

On the Mechanism and Origin of Isoleucyl-tRNA Synthetase Editing against Norvaline.
Journal of Molecular Biology. 2019, doi:10.1016/j.jmb.2019.01.029
Bilus Mirna; Semanjski Maja; Mocibob Marko; Zivkovic Igor; Cvetesic Nevena; Tawfik S. Dan; Toth-Petroczy Agnes; Macek Boris; Gruic Sovulj Ita

Arabidopsis seryl‐tRNA synthetase: the first crystal structure and novel protein interactor of plant aminoacyl‐tRNA synthetase
The FEBS Journal. 286 (2019), 3;536-554
Kekez Mario; Zanki Vladimir; Kekez Ivana; Baranasic Jurica; Hodnik Vesna; Duchene Anne-Marie; Anderluh Gregor; Gruic Sovulj Ita; Matković-Čalogović Dubravka; Weygand Durasevic Ivana; Rokov-Plavec Jasmina

Kinetic Origin of Substrate Specificity in Post-Transfer Editing by Leucyl-tRNA Synthetase.
Journal of Molecular Biology. 430 (2018), 1; 1-16
Dulic Morana; Cvetesic Nevena; Zivkovic Igor; Palencia Andrés; Cusack Stephen; Bertosa Branimir; Gruic Sovulj Ita

An archaeal aminoacyl-tRNA synthetase complex for improved substrate quality control.
Biochimie. 147 (2018), 1; 36-45
Crnković Ana, Čavužić Mirela, Godinić-Mikulčić Vlatka, Anderluh Gregor, Weygand-Đurašević Ivana, Gruić-Sovulj Ita

Discovery and Investigation of Natural Editing Function against Artificial Amino Acids in Protein Translation.
ACS Central Science. 3 (2017), 1; 73-80
Voeller Jan-Stefan; Dulic Morana; Gerling-Driessen Ulla I. M.; Biava Hernan; Baumann Tobias; Budisa Nediljko; Gruic Sovulj Ita; Koksch Beate

Synthetic and editing reactions of aminoacyl-tRNA synthetases using cognate and non-cognate amino acid substrates.
Methods. 113 (2017) 13-26
Cvetesic Nevena; Gruic Sovulj Ita.

Proteome-wide measurements of non-canonical mistranslation by quantitative mass spectrometry of protein modifications.
Scientific Reports. 6:28631.
Cvetesic Nevena; Semanjski Maja; Soufi Boumediene; Krug Karsten, Gruic Sovulj Ita; Macek Boris.

Naturally Occuring Isoleucyl-tRNA Synthetase without tRNA-dependent Pre-transfer Editing.
The Journal of biological chemistry. 291 (2016), 16; 8618-8631 
Cvetesic Nevena; Dulic Morana; Bilus Mirna; Sostaric Nikolina; Lenhard Boris; Gruic Sovulj Ita.

The origin of specificity and insight into recognition between an aminoacyl carrier protein and its partner ligase.
Physical Chemistry Chemical Physics. 17 (2015), 29; 19030-19038
Marsavelski Aleksandra; Mocibob Marko; Gruic-Sovulj Ita; Vianello Robert.

The tRNA A76 Hydroxyl Groups Control Partitioning of the tRNA-dependent Pre- and Post-transfer Editing Pathways in Class I tRNA Synthetase.
The Journal of biological chemistry. 290 (2015), 22; 1398-1391 
Cvetesic Nevena; Bilus Mirna; Gruic-Sovulj Ita.

The physiological target for LeuRS translational quality control is norvaline. 
EMBO journal. 33 (2014), 15; 1639-1653
Cvetesic Nevena; Palencia Andres; Halasz, Ivan; Cusack Stephen; Gruic-Sovulj Ita.

Synthetic and Editing Mechanisms of Aminoacyl-tRNA Synthetases. 
Topics in current chemistry. 344 (2014) ; 1-42 
Perona John J.; Gruic-Sovulj Ita.

Lack of discrimination against non-proteinogenic amino acid norvaline by elongation factor Tu from Escherichia coli. 
Croatica chemica acta. 86 (2013), 1; 73-82 
Cvetesic Nevena; Akmacic Irena; Gruic-Sovulj Ita.

Substrate recognition and fidelity of maize seryl- tRNA synthetases. 
Archives of biochemistry and biophysics. 529 (2013), 2; 122-130
Rokov-Plavec Jasmina; Lesjak Sonja; Gruic-Sovulj Ita; Mocibob Marko; Dulic Morana; Weygand-Durasevic Ivana.

Kinetic Partitioning between Synthetic and Editing Pathways in Class I Aminoacyl-tRNA Synthetases Occurs at Both Pre-transfer and Post-transfer Hydrolytic Steps.
The Journal of biological chemistry. 287 (2012), 30; 25381-25394
Cvetesic Nevena; Perona John J; Gruic-Sovulj Ita.

An idiosyncratic serine ordering loop in methanogen seryl-tRNA synthetases guides substrates through seryl-tRNASer formation. 
Biochimie. 93 (2011), 10; 1761-1769
Dulic Morana; Pozar Josip; Bilokapic Silvija; Weygand-Durasevic Ivana; Gruic-Sovulj Ita.

Pre-transfer editing of serine hydroxamate within the active site of methanogenic-type seryl-tRNA synthetase. 
Croatica chemica acta. 84 (2011), 2; 179-184
Gruic-Sovulj Ita; Dulic Morana; Weygand-Durasevic Ivana.

Partitioning of tRNA-dependent Editing between Pre- and Post-transfer Pathways in Class I Aminoacyl-tRNA Synthetases. 
The Journal of biological chemistry. 285 (2010), 31; 23799-23809
Dulic Morana; Cvetesic Nevena; Perona, John J; Gruic-Sovulj Ita.

Efficiently activated serine analogue is not transferred to yeast tRNASer. 
Croatica chemica acta. 83 (2010), 2; 163-169
Gruic-Sovulj Ita; Dulic Morana; Jaric Jelena; Cvetesic Nevena; Majsec Kristina; Weygand-Durasevic Ivana.

Differences between reversible (self-association) and irreversible aggregation of rHuG-CSF in carbohydrate and polyol formulations. 
European journal of pharmaceutics and biopharmaceutics. 76 (2010), 3; 357-365
Pavisic Renata; Dodig Ivana; Horvatic Anita; Mijic Lucija; Sedic Mirela; Rajic Linaric Masa; Gruic Sovulj Ita; Preocanin Tajana; Bukvic Krajacic Mirjana; Cindric Mario.

Synthesis and Biological Activity of Mannose Conjugates with 1-Adamantamine and Ferrocene Amines. 
Croatica chemica acta. 83 (2010), 4; 421-431
Ribic Rosana; Kovacevic Monika; Petrovic Perokovic Vesna; Gruic-Sovulj Ita; Rapic Vladimir; Tomic Srdanka.

Hydrolysis of non-cognate aminoacyl-adenylates by a class II aminoacyl-tRNA synthetase lacking an editing domain. 
FEBS Letters. 581 (2007), 26; 5110-5114
Gruic-Sovulj Ita; Rokov-Plavec Jasmina; Weygand-Durasevic Ivana.

Shuffling of Discrete tRNASer Regions Reveals Differently Utilized Identity Elements in Yeast and Methanogenic Archaea. 
Journal of molecular biology. 361 (2006), 1; 128-139
Gruic-Sovulj Ita; Jaric Jelena; Dulic Morana; Cindric Mario; Weygand-Durasevic Ivana.

Structure of the unusual methanogen seryl-tRNA synthetase reveals a distinct zincdependent mode of substrate recognition. 
EMBO Journal. 25 (2006.), 11; 2498-509
Bilokapic, Silvija; Maier, Timm; Ahel, Dragana; Gruic-Sovulj, Ita; Söll, Dieter; Weygand-Durasevic, Ivana; Ban, Nenad.

tRNA-dependent aminoacyl-adenylate hydrolysis by a nonediting class I aminoacyl-tRNA synthetase. 
The Journal of biological chemistry. 280 (2005.) ; 23978-23986
Gruic-Sovulj Ita; Uter Nathan; Bullock Timothy; Perona John.

Amino acid-dependent transfer RNA affinity in a class I aminoacyl-tRNA synthetase.
The Journal of biological chemistry. 280 (2005.); 23966-23977
Uter Nathan; Gruic-Sovulj Ita; Perona John.

Stability of the complex between yeast seryl-tRNA synthetase and tRNASer under different electrophoretic conditions.
Croatica Chemica Acta. 77 (2004), 4; 1643-1650
Gruic-Sovulj Ita; Rokov-Plavec Jasmina; Mocibob Marko; Kamenski Tomislav; Weygand-Durasevic Ivana.

tRNA-dependent amino acid discrimination by yeast seryl-tRNA synthetases. 
European journal of biochemistry. 269 (2002) ; 5271-5279
Gruic-Sovulj, Ita; Landeka, Irena; Söll, Dieter; Weygand-Durasevic, Ivana.

The accuracy of seryl-tRNA synthesis. 
Food technology and biotechnology. 40 (2002) ; 247-253
Weygand-Durasevic Ivana; Gruic-Sovulj Ita; Rocak Sanda; Landeka Irena.

Influence of modified tRNATyr on the activation of tyrosine catalyzed by tyrosyl-tRNA synthetase from Saccharomyces cerevisiae. 
Croatica Chemica Acta. 74 (2001), 1; 161-171
Gruic-Sovulj Ita; Weygand-Durasevic Ivana; Kucan Zeljko.

Detection of noncovalent tRNA-aminoacyl-tRNA synthetase complexes by matrix-assisted laser desorption/ionization mass spectrometry. 
Journal of biological chemistry. 272 (1997), 51; 32084-32091
Gruic-Sovulj Ita; Luedemann Hans-Christian; Hillenkamp Franz; Weygand-Durasevic Ivana; Kucan, Zeljko; Peter-Katalinic Jasna.

Matrix-assisted laser desorption/ionisation mass spectrometry of transfer ribonucleic acids isolated from yeast. 
Nucleic acids research. 25 (1997), 9; 1859-1861
Gruic-Sovulj Ita; Luedemann Hans-Christian; Hillenkamp Franz; Weygand-Durasevic Ivana; Kucan Zeljko; Peter-Katalinic Jasna.