Mariusz Jaskólski
Professor, Department of Crystallography,
Faculty of Chemistry,
A.Mickiewicz University
(UAM)
and Department of Structural Biology of Eukaryotes,
Institute of Bioorganic Chemistry,
Polish Academy of Sciences
Polish Academy of Sciences Ordinary Member,
EMBO member
Tel.: +48-61-829-1274
Fax: +48-61-852-0532
Email:
mariuszj@amu.edu.pl
Degrees
- 1985 - D.Sc. - physical chemistry and crystallography, UAM
- 1979 - Ph.D. - chemistry, UAM
- 1976 - M.Sc. - chemistry, UAM
Previous posts
- Visiting Scientist, Macromol. Struct. Lab., NCI-FCRDC (USA)
- Head, Center for Biocrystallographic Research, IBCH PAN
Honors
- Swietoslawski Award, Polish Academy of Sciences (1976)
- Trzebiatowski Award, Polish Academy of Sciences (1988)
- International Research Scholar of the Howard Hughes Medical Institute (1994-2002)
- Corresponding Member of the Polish Academy of Sciences (elected 2002)
- Prize of the Foundation for Polish Science (FNP) (2002)
- Zawidzki Medal, awarded by Polish Chemical Society (2003)
- Faculty Scholar, NCI (appointed 2004)
- Member of the European Molecular Biology Organization (elected 2004)
- Foreign Member, The Royal Society of Sciences at Uppsala (elected 2005)
- Parnas Award, awarded by Polish Biochemical Society (2006)
- Marchlewski Medal, awarded by Committee of Biochemistry and Biophysics, Polish Academy of Sciences (2009)
- Poland-U.S. Science Award (together with A. Wlodawer), awarded by American Association for the Advancement of Science (AAAS) and Foundation for Polish Science (FNP) (2015)
- Sniadecki Medal, awarded by Polish Chemical Society (2015)
- Crystallographic Diamonds, Committee of Crystallography, Polish Academy of Sciences (2016)
- Ordinary Member of the Polish Academy of Sciences (elected 2016)
- Prize of the Polish Crystallographic Association (2017)
- Bassalik Award, awarded by Committee of Molecular Biology of the Cell, Polish Academy of Sciences (2020)
- Crystallographic Diamonds, Committee of Crystallography, Polish Academy of Sciences (2021)
- Two awards of Crystallographic Diamonds, Committee of Crystallography, Polish Academy of Sciences (2022)
- Scientific Award of the Prime Minister of the Republic of Poland (2022)
- Polish Synchrotron Radiation Society (PTPS) Award for best scientific publication based on SR (2023)
- Two independent Crystallographic Diamonds, Committee of Crystallography, Polish Academy of Sciences (2023)
- Medal of the Commission of National Education (KEN, Republic of Poland, 2024)
- Max Perutz Prize (European Crystallographic Association, 2024)
Postal address
Department of Crystallography
Faculty of Chemistry
A.Mickiewicz University
Uniwersytetu Poznanskiego 8
61-614 Poznan, Poland
Current research interests and achievements
My main field of expertise is crystallography. I have applied the
techniques of crystal structure determination to study the following
problems of structural chemistry and structural biology.
- Retroviral protease. In collaboration with Dr. Alex Wlodawer
(NCI-FCRDC), the structure of the first retroviral
protease (from Avian sarcoma virus) and of the (chemically synthesized)
protease from HIV-1 have been determined showing that these enzymes
belong to the class of aspartic proteases and establishing firm
foundations for rational design of anti-AIDS drugs targeted at the
maturation process of the HIV virus. Also, a complex of HIV-1
protease inactivated by a substrate-based inhibitor has been analyzed
and a new view on the catalytic mechanism of retroviral proteases has
been proposed. The first crystal structure of monomeric subunit of a retroviral
protease (from Mason-Pfizer monkey virus, M-PMV) has been determined using a
model built by players of the on-line game Foldit.
- Retroviral integrase. The crystal structure determined (together
with Dr. Alex Wlodawer, NCI-FCRDC, and Dr. Anne Skalka, FCCC) for
the catalytic domain of Avian sarcoma virus integrase revealed,
for the first time, the complete and ordered active site of the enzyme
as well as the location and possible role of the divalent cations which
are required cofactors for the integration reaction.
- Bacterial asparaginases. The first structure of a bacterial
asparaginase, EcAII from E. coli (a drug used in cancer therapy), was
determined in collaboration with Dr. A. Wlodawer (NCI, USA). It allowed the identification of the active site,
formed grounds for structure-based discussions of the catalytic
mechanism, and provided a reliable model for numerous structures of bacterial
asparaginase/glutaminases. Subseqent studies focused on mutants
of the bacterial enzymes and on a different class of L-asparaginases found in plants (but also present in other kingdoms of life). More recently,
the structure of yet another class of L-asparaginases, originally found in the symbiotic bacterium Rhizobium etli, has been determined, showing
an enzyme unlike any other known L-asparaginases, with an active site built around two Ser-Lys tandems, and with a curiously coordinated Zn ion
that does not have a catalytic role.
- Ntn hydrolases. A plant asparaginase (LlA) has been sequenced, cloned,
expressed and crystallized. Its close analog (EcAIII) has been found in the E. coli
genome. The structures of these proteins reveal that they are Ntn
hydrolase. It has been found that in addition to their predicted asparaginase
activity, they have more potent isoaspartyl aminopeptidase activities, but are
inactive towards glycosylasparagine despite high sequence similarity to
aspartylglucosaminidases. The crystal structure of an active-site mutant
of EcAIII suggests a mechanism for the autocatalytic activation reaction. In variance with LlA and EcAIII, which despite their binding of sodium in a Stabilization Loop are insensitive
to alkali metal concentration, the K-dependent enzyme from common bean (PvAK) is activated by potassium cations. Our structural dissection of this protein in complexes with Na+ and K+
cations reveals an additional alkali-metal binding site (Activation Loop), which changes conformation upon Na/K exchange, setting a switch of three crucial residues to an OFF or ON
state.
- Pathogenesis-related proteins. The crystal structures of several
homologs from the multi-gene family of plant pathogenesis-related
proteins of class 10, reveal their similarity to common pollen allergens
and suggest how they could bind small-molecule ligands. Among the studied
proteins are those originally described as CSBP, i.e. specific binders of cytokinins, which are a class of plant hormones. The structure
of a representative of these proteins (from V. radiata) determined at atomic resolution in complex with
the classic cytokinin hormone trans-zeatin, revealed a puzzling
dual mode of ligand binding. Subsequently, we found that the CSBP proteins are much stronger binders of gibberellic acid, which is an entirely different plant hormone. The CSBP subfamily
has been accordingly renamed PhBP (phytohormone binding proteins) to better reflect the biological activity. In contrast, nodulin 13 from M. truncatula (MtN13) binds various
cytokinins very specifically but only in an unusual homodimeric form. Hyp-1, which is a PR-10 protein from St John's wort, in complex with the fluorescent dye ANS, forms
unusual crystals that have modulated superstructure with 28 or even 36 protein molecules in the asymmetric unit. Hyp-1, and later LlPR-10.2B from yellow lupine were also
demonstrated to bind melatonin, providing the first structural insight into protein complexes of this emerging plant hormone.
- Cysteine proteases. Proteases in this family play a role in
degenerative diseases, such as osteoporosis or muscular dystrophy. In
our search of new compounds that could be used as drugs, we have determined
the crystal structure of several complexs between the cysteine protease
papain and different inhibitors (irreversible and peptidic) designed
after the natural inhibitors, E-64 and human cystatin C. In addition, we determined
the structure of the cysteine-protease inhibitor chagasin from Trypanosoma cruzi,
the pathogenic protozoan that causes Chagas disease, both in its enzyme-free form
and in complex with human cathepsins L and B, and with papain.
- Amyloidogenic proteins. Amyloid-forming proteins attract
attention because of their role in the pathogenesis of several
"conformational" diseases, like Alzheimer's disease and the prionoses.
Human cystatin C, a potent and abundant protease inhibitor, is known to
undergo pathological dimerization, and at advanced age forms
amyloid deposits in the brain arteries. This tendency to aggregate is
drastically amplified in the endemically occurring L68Q mutant. We have
solved the crystal structure of human cystatin C in its dimeric form
and demonstrated that the protein aggregates through exchange of
structural units, in a process known as 3D domain swapping. The hinge
allowing the protein to partially unfold and to refold in higher
oligomeric state is part of the enzyme-binding epitope, which makes the
dimer physiologically inactive as inhibitor of papain-class enzymes. The
protein undergoes 3D domain swapping both in its full-length form and as an
N-truncated peptide, which is the main product extracted from in vivo amyloid
fibrils. In one of the crystal forms, the dimeric protein undergoes further
aggregation via intermolecular beta sheets reminiscent of the cross-beta
structure believed to exist in amyloid fibrils. Specific mutagenesis directed
towards creating new disulfide bridges that would prevent domain swapping
inhibits the dimerization process completely and greatly reduces the protein's
ability to form amyloid fibrils in vitro. Dimerization can also be supressed
by binding of exogenous agents, such as carboxymethylpapain or a monoclonal
antibody.
- Structural chemistry of nucleic acids and their constituents. The
structure of a number of nucleosides and their salts have been
determined leading to a better understanding of the behavior of
protonated vs. neutral nucleosides. The structures of phosphate
salts of nucleosides revealed their structural preferences and
opened new avenues for crystal engineering of nucleic acids
constituents. Also the structure of several exotic forms of DNA and RNA has been studied with very high accuracy and precision. We hold the record of the highest-resolution
(0.55 A) Z-DNA structure in the PDB. We have compiled the RestraintLib library of revised stereochemical
restraints for nucleic acids that can be used with most of the popular refinement programs.
- Hydrogen bonding in solids. Several systems with very short
O...O, N...O and N...N hydrogen bridges have been studied, including the
so-called proton-sponges, also in deuterated form and in extremely low
temperatures. Correlations of the parameters describing the D-H...A system
have been discussed and a limit for the D-H...A angle has been proposed. In
addition to extremely strong hydrogen bonds, C-H...A bonds and other
non-classical interactions are also studied.
- Validation of macromolecular models. A number of campaigns have been carried out to check the quality and correctness of PDB models, especially with focus on
medicinal applications. Validation of crystallographic models is based on two principles: agreement with and support from the electron density, and agreement with prior structural
knowledge. Of particular interest is validation of small-molecule ligands as they often are studied as potential drug-design leads. As a result of our actions, a number of PDB models have
been corrected, retracted, or superseded. An example of such a campaign is the validation of structure models of SARS-CoV-2 proteins, summarized in covid.bioreproducibility.org.
- Teaching. I have taught crystallography
for many years. Recent courses focus on structural biology and macromolecular crystallography.
A textbook
"Krystalografia dla biologow"
("Crystallography for Biologists") is a summary of my lecture course taught to biology students (in Polish).
Some didactic presentations,
a crystallographic quiz,
a movie on Protein
Crystallization,
and
"Crystallographic ABC" are freely available.
Lists available for viewing
YouTube clips and movies
Recent research support
-
National Science Centre OPUS-19 grant for
Novel L-asparaginases as potential therapeutic agents and antimicrobial targets: structural and functional studies
of enzymes with dual implications for drug design
-
National Science Centre COVID-19 grant for
Validation of PDB models of potential drug design targets for SARS-CoV-2 coronavirus
Last update: May 18, 2024
photo by Kay Chernush