Maria Hrmova

Maria Hrmova

School of Agriculture, Food and Wine

Faculty of Sciences, Engineering and Technology

Professional interests: My expertise is in the multidisciplinary field of structural biochemistry and biophysics.

Research in my group resulted in the publishing of around 220 peer-reviewed articles and patents explaining catalytic mechanisms of enzymes in crop plants, and the roles of transporters and transcription factors in plant abiotic stress tolerance. Our outputs have appeared in the top-tier journals Nature Communications, Science, Cell Research, Communications Biology, American Chemical Society, Biotechnology Advances, Current Opinion in Plant Biology, Biochemical Society Transactions, Plant Cell, Plant Physiology, Plant Journal, Biochemical Journal, Journal of Biological Chemistry, etc. Our works have received ~8,000 citations and 14 papers have been featured on the front covers of academic resources.

My group investigates molecular mechanisms that underpin the function of plant proteins in three major areas:

(i) CATALYTIC MECHANISMS OF ENZYMES INVOLVED IN PLANT DEVELOPMENT
We focus on catalytic mechanisms of plant exohydrolytic and xyloglucan xyloglucosyl transferase enzymes. With exohydrolases using high-resolution X-ray crystallography, enzyme kinetics, mass spectrometry, NMR spectroscopy, and multi-scale 3D molecular modelling, we discovered the glucose product displacement mechanism and how it is linked to the catalytic cycle. This newly described ‘substrate-product assisted processive catalytic’ mechanism represents a series of events, where on productive substrate binding near the active site, the entrapped glucose product modifies its binding patterns and evokes the formation of a temporary lateral cavity, which serves as a conduit for glucose departure to allow for the next catalytic cycle. This path enables efficient catalysis via multiple hydrolytic events without the enzyme losing contact with oligo- or polysaccharides. This discovery has significance in biotechnology to engineer enzymes for how plant materials can be converted into biofuels, biochemicals and other high-value products. It is also applicable in the pharmaceutical industry, where enzymes are sought as environmentally friendly and cost-effective options in bioremediation, and other applications. This work was published in two articles in Nature Communications.

With xyloglucan xyloglucosyl transferases we engineered the acceptor substrate specificity in nasturtium enzymes and in barley isoforms we discovered that they catalysed the covalent bond formation between the xyloglucan donor and the penta-galacturonide acceptor – the homogalacturonan (pectin) fragment. This work was published in Plant Molecular Biology, and Plant Journal.

(ii) PLANT TRANSPORT PROTEINS UNDERLYING ELEMENTAL SOIL TOXICITY TOLERANCE
My laboratory is focused on the structural and functional properties of plant borate and HKT (High-affinity Potassium Transporter) Na+/K+ transporters and unorthodox and multifunctional aquaporins. By combining in silico and in vitro methods, we discovered that borate transporters mediate Na+-dependent anion transport and exhibit channel-like characteristics. This work was published in Plant Cell, and Plant Physiology.

With HKT transporters, we constructed the 3D structural model for Na+-exclusion in rice and explained that variations in salt tolerance can be explained by transcription, alternative splicing, and a protein structure. We clarified a long-standing question, how do the structural variations in wheat HKT proteins underpin differences in Na+ transport capacity; this work was highlighted on the front cover of Cellular and Molecular Life Sciences and published in Plant Cell & Environment, and Communications Biology.

(iii) TRANSCRIPTION FACTORS INVOLVED IN THE REGULATION OF PLANT RESPONSES TO DROUGHT
We perform extensive 3D molecular modelling studies of transcription factors in complex with DNA cis-elements, such as bZIP, HDZip, DREB, ERF, NFY-YB, CBF, and MYB, and validate these DNA-binding properties in vitro. We engineered wheat transcription factor variants and in breakthrough science, using genetically engineered plants, we showed that these modifications changed DNA recognition and plant responses to drought and frost. Our work was highlighted on the front covers of Plant Biotechnology Journal, Plant Molecular Biology, and Journal of Experimental Botany.

Using a combination of biology, biochemistry, biophysics, bioinformatics, and computational chemistry techniques, including multi-scale molecular modelling of nanoscale reactant movements in a plant exohydrolytic enzyme, we have discovered a remarkable phenomenon during initial and final catalytic events near the surface of this enzyme. The enzyme formed a transient cavity, which allowed the trapped glucose product to escape to allow for the next round of catalysis. This path enables "substrate-product assisted processive catalysis" through multiple hydrolytic events without the enzyme losing contact with oligo- or polymeric substrates. We anticipate that such enzyme plasticity could be prevalent among exo-hydrolases.

Our discovery of substrate-product-assisted processive catalysis has significance for the multibillion-dollar biomedical, pharmaceutical, chemical, and biotechnology industries to engineer enzymes that could be used efficiently outside of biological systems.

Structural changes of a barley enzyme envisaged by high-resolution X-ray crystallography and multiscale molecular modelling.

Legend to the image: Structural changes of a barley enzyme envisaged by high-resolution X-ray crystallography and multiscale molecular modelling.

This work was published in two articles in Nature Communications.

Streltsov VA, Luang S, Peisley A, Varghese JN, Ketudat Cairns JR, Fort S, Hijnen M, Tvaroška I, Ardá A, Jiménez-Barbero J, Alfonso-Prieto M, Rovira C, Mendoza F, Tiessler-Sala L, Sánchez-Aparicio S-E, Rodríguez-Guerra J, Lluch JM, Maréchal J-D, Masgrau L, Hrmova M* (2019) Discovery of processive catalysis by an exo-hydrolase with a pocket-shaped active site. Nature Communications 10 (2222); https://doi.org/10.1038/s41467-019-09691-z. *Corresponding author.

Luang S, Fernández-Luengo X, Nin-Hill A, Streltsov VA, Schwerdt JG, Alonso-Gil S, Ketudat Cairns JR, Pradeau S, Fort S, Maréchal J-D, Masgrau L, Rovira C, Hrmova M* (2022) The evolutionary advantage of an aromatic clamp in plant family 3 glycoside exo-hydrolases. Nature Communications 13 (5577); https://doi.org/10.1038/s41467-022-33180-5. *Corresponding author.

Press Releases for these articles can be seen here (https://phys.org/news/2019-05-discovery-frontiers.html and https://www.thewaite.org/ultra-fast-plant-enzyme-dynamics-leads-to-breakthroughs/).

Movies describing the newly discovered catalytic mechanism can be seen here (https://figshare.com/articles/media/Streltsov-et-al_movie_mp4/8075504 and https://figshare.com/s/faf4d4d8c582ed0d7184).

Movie descriptions:

Movie 1    Nature Communications 2019, 10 (2222)

Molecular animation of the sequence of events involving the glucose product entrapment, incoming substrate binding, and glucose displacement in a plant exo-hydrolase HvExoI, and how this sequence of events underlies substrate-product assisted processive catalysis. The movie shows the entrapped glucose molecule in the -1 subsite of the active site, through twelve residues located on seven loops. After the incoming β-D-glucopyranosyl-(1,3)-D-glucose substrate binds in the +1 and putative +2 subsites, the glucose product adjusts its binding patterns and traverses from the -1 subsite through rotations of Arg158 and Asp285 sidechains and associated backbone atoms, into the autonomous and transient lateral cavity, from where it advances through the aperture into the bulk solvent. The video was prepared in Chimera (Pettersen, E. F. et al. J. Comput. Chem. 25, 1605-1612; 2004), using the HD Movie Maker tool.

Movie 2    Nature Communications 2022, 13 (5577)

Molecular animation of sequences of events in wild-type HvExoI after the laminarihexaose substrate is hydrolysed into Glc and laminaripentaose (L5). Here, the Glc product adjusts its binding patterns and traverses from the -1 subsite through rotations of Arg158, Tyr253, Asp285, Glu491 sidechains, and associated backbone atoms into the autonomous and transient lateral cavity, from where it advances through the ad-hoc formed aperture into bulk solvent. These are key events of path 1 of substrate-product-assisted processive catalysis. The video was prepared as described in the legend for Movie 1.

Movie 3    Nature Communications 2022,13 (5577)

Molecular animation of sequences of events in the W434H mutant of HvExoI after the laminarihexaose substrate is hydrolysed into Glc and laminaripentaose (L5). Here, the Glc product adjusts its binding patterns and traverses from the -1 subsite through rotations of Arg158, Tyr253, Asp285, Glu491 sidechains, and associated backbone atoms into the autonomous and transient lateral cavity, from where it advances through the ad-hoc formed aperture into bulk solvent. These are key events of path 1 of substrate-product-assisted processive catalysis. The video was prepared as described in the legend for Movie 1.

Movie 4    Nature Communications 2022,13 (5577)

Molecular animation of sequences of events in the W434A mutant of HvExoI after the laminarihexaose substrate is hydrolysed into Glc and laminaripentaose (L5). Here, the Glc product diffuses through the preformed opening resulting from the W434A mutation. In this Glc egress path, the toll-like Arg158-Asp285-Glu491 barrier, Tyr253, and the Arg291-Glu220 salt bridge are not involved. These are key events of path 2, where substrate-product-assisted processive catalysis does not take place. The video was prepared as described in the legend for Movie 1.

  • Appointments
    Date Position Institution name
    2010 - ongoing Professor (Research) University of Adelaide

  • Awards and Achievements
    Date Type Title Institution Name Country Amount
    2023 Award COMMEMORATIVE MEDAL OF THE INSTITUTE OF CHEMISTRY OF THE SLOVAK ACADEMY OF SCIENCES THE INSTITUTE OF CHEMISTRY OF THE SLOVAK ACADEMY OF SCIENCES Slovakia -
    2021 Award THE GOLD MEDAL OF THE SLOVAK ACADEMY OF SCIENCES THE SLOVAK ACADEMY OF SCIENCES Slovakia -
    2019 Award PROFESSOR EMERITA AT THE UNIVERSITY OF ADELAIDE The University of Adelaide Australia -
    2012 Award ELECTED MEMBER OF THE LEARNED SOCIETY OF SLOVAK ACADEMY OF SCIENCES Comenius University Slovakia -
    2012 Award DOCTOR SCIENTIARUM BY THE COMENIUS UNIVERSITY, SLOVAK REPUBLIC THE COMENIUS UNIVERSITY Slovakia -

  • Language Competencies
    Language Competency
    Czech Can read, write, speak, understand spoken and peer review
    English Can read, write, speak, understand spoken and peer review
    German Can read, write and understand spoken
    Slovak Can read, write, speak, understand spoken and peer review

  • Education
    Date Institution name Country Title
    2010 - 2012 Comenius University Slovakia Doctor Scientiarum (DrSci) in Chemistry
    1978 - 1981 Comenius University in Bratislava Slovakia Philosophy Doctor (PhD) in Biochemistry
    1976 - 1978 Comenius University Slovakia Master of Science (MSc) in Biochemistry
    1974 - 1975 Comenius University Slovakia Bachelor of Science (BSc) in Biochemistry

  • Certifications
    Date Title Institution name Country
    2023 The commemorative medal Institute of Chemistry of the Slovak Academy of Sciences Slovakia
    2021 The recipient of the Gold Medal of Slovak Academy of Sciences Slovak Academy of Sciences Slovakia
    2019 Professor Emerita UNIVERSITY OF ADELAIDE Australia
    2012 Doctor Scientiarum Comenius University in Bratislava Slovakia
    2012 An elected member of the Learned Society of Slovak Academy of Sciences SLOVAK ACADEMY OF SCIENCES SLovakia

  • Research Interests
    Biocatalysis and Enzyme Technology Biochemistry & Molecular Biology Biomolecular Modelling and Design Biophysics Molecular Evolution Structural Biology Theoretical and Computational Chemistry

Research in my laboratory has been funded by grants from the Australian Research Council, by the Grains Research & Development Corporation, the South Australian Government, the Waite Research Institute of the University of Adelaide, DuPont Pioneer and by the Australian Synchrotron Research Program. The latter is supported by the Commonwealth of Australia under the Major National Research Facilities Program.

I have successfully completed supervisions of 25 doctoral (PhD), masters (MSc) and honours (BSc) candidatures by research. My students have received a variety of awards: Best Presentation in Plant Science and runner up for the Max Tate Award (in-house Annual Postgraduate Symposium), People’s Choice (3-minute PhD thesis competition), Travelling Scholarship to Cambridge University (Barr Smith Foundation), the KP Barley Prize for PhD thesis excellence (Faculty of Sciences), and CJ Everald and GRDC top-up scholarships.

  • Past Higher Degree by Research Supervision (University of Adelaide)
    Date Role Research Topic Program Degree Type Student Load Student Name
    2012 - 2016 Co-Supervisor Characterization of Wheat Cuticle and Wheat Cuticle-Related Transcription Factor Genes in Relation to Drought Doctor of Philosophy Doctorate Full Time Miss Huihui Bi
    2011 - 2015 Principal Supervisor Structural and functional properties of a borate efflux transporter from barley Doctor of Philosophy Doctorate Full Time Dr Yagnesh Nagarajan
    2008 - 2017 Co-Supervisor The Evolutionary History and Dynamics of the Cellulose Synthase Superfamily Doctor of Philosophy Doctorate Full Time Dr Julian Schwerdt
    2004 - 2008 Co-Supervisor Characterisation of PpMDHARs and PpENA1 From the Moss, Physcomitrella patens Doctor of Philosophy Doctorate Full Time Mr Damian Drew
    1997 - 2002 Co-Supervisor Biochemistry and Molecular Biology of Arabinoxylan Metabolism in Barley Doctor of Philosophy Doctorate Full Time Mr Robert Lee
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