Attila Jancsó's Homepage

Presently running projects
- Metalloregulatory proteins Many metal ions, including transition metal ions play important roles in biochemical processes. There are others, however, that are toxic for all living organisms. Even the essential metal ions can induce adverse effects when their concentration exceeds an optimal concentration range. It is essential for all living organisms to control the concentration of metal ions and to operate detoxification systems against the toxic constituents. The homeostatic metal ion balance is ensured by the ensemble of various transportation, transformation, storage and regulation processes. Metal ion sensing regulatory proteins, operating at the level of genetic transcription, play a fundamental role in bacterial metal ion homeostasis. These metalloregulatory proteins respond to the change of metal ion concentration by inducing or repressing the expression of proteins that participate in processes that balance the level of the regulated metal ion. Our research focuses mainly on members of the large MerR and ArsR protein families, but most importantly our main goal is to better understand the metal ion selective mechanism of operation of the copper efflux regulator CueR. Our studies involve experiments on the metal ion interaction of model peptides inspired by the metal binding loops these metalloregulators, but also the investigation of the metal ion binding features of the native proteins and their carefully designed mutants. The metal ion regulating/sensing mechanisms of the studied proteins may also be exploited for the design of genetically modified bacteria that (over)produce fluorescent proteins in a metal-ion promoted event and thus may signal the presence or even the change of concentration of a specific metal ion.	Overall structure highlighting the major domains of the CueR protein (left) and its metal ion binding loop (right) (PDB: 1q05) Experimentally determined structure of CueR-Ag^I (pink, PDB 1q06) overlaid with the geometry optimized structures of the metal ion binding site involving the coordinated Cys112 residue in its protonated (right) or deprotonated form (left) D. Szunyogh, H. Szokolai, P.W. Thulstrup, F.H. Larsen, B. Gyurcsik, N.J. Christensen, M. Stachura, L. Hemmingsen, A. Jancsó, "Specificity of the Metalloregulator CueR for Monovalent Metal Ions: Possible Functional Role of a Coordinated Thiol?", Angew. Chem. Int. Ed., 54, 15756-15761 (2015).

- Peptides as potential metal ion sensors Heavy metal ions appear in the environment from natural or anthropogenic sources and present a hazard to all living organisms. The development of novel methods that allow the sensitive, fast, simple, sometimes even on-site determination of such contaminants, and thus being real alternatives to the robust, lab-based instrumental techniques, is in the focus of environmental/(bio)analytical research. Our research aims at the design and investigation of oligopeptides with efficient toxic (semi)metal ion binding abilities that may potentially act as metal ion receptors in optochemical sensors. The sequences of these ligands have been inspired by the metal ion binding sites of various metalloproteins with transport, chaperone or regulatory functions. The ligands are synthesized with fluorophore labels allowing the optical detection of metal ion binding. Besides, we are also aiming at the synthesis and investigation of such molecular probes in their immobilized, solid-supported forms (attached to a resin, glass or quartz surface).	Hg²⁺ és Cd²⁺ binding scheme of a fluorescent hexapeptide, containing two cysteine units, under acidic (pH = 2.0) and slightly acidic (pH = 6.0) conditions at solution phase and in a resin-attached immobilized form L.I. Szekeres, S. Bálint, G. Galbács, I. Kálomista, T. Kiss, F.H. Larsen, L. Hemmingsen, A. Jancsó, “Hg²⁺ and Cd²⁺ binding of a bioinspired hexapeptide with two cysteine units constructed as a minimalistic metal ion sensing fluorescent probe”, Dalton Trans., 48, 8327-8339 (2019).

- Interaction of As^III (and Sb^III) with thiol ligands: biospeciation, biochemical effects, chelator development Arsenic is known to exert severe biological effects on cells and tissues depending on the level and duration of exposure. As an interesting contrast arsenic and its derivatives have been applied, since the ancient times, as therapeutic agents e.g. in the treatment of ulcers, plague or malaria. Most significantly, arsenic trioxide (As₂O₃) has been shown to possess important antitumor properties against human acute promyelocytic leukemia (APL). It was suggested that similar mechanisms may operate both in the therapeutic and toxic activities of arsenic, nevertheless, the molecular details of these mechanisms are yet to be explored. It is well known, that arsenic, in its trivalent oxidation state, can bind to reduced thiols, especially when more thiol groups are available, and this plays a role in many of its physiological effects. Nevertheless, solution speciation studies on the systems of As^III and small multithiol ligands are scarce in the literature, even though understanding the As^III-thiol interaction at the level of small models could be essential in unravelling the versatile, sometimes paradoxical biological effects. With an aim of exploring the possible binding site and coordination environment preferences of As^III in biological milieu we investigate the interactions of arsenous acid (H₃AsO₃ - the typical aqueous form of As^III) with several thiol ligands, including heavy metal ion chelators and peptides.	Identification of a species formed by the binding of two thiol and an alcoholic hydroxi group in the arsenous acid - dimercaprol (British anti-Lewisite - BAL) system by using NMR spectroscopy Simulated species distribution curves as a function of the As^III:BAL concentration ratio an structures of the monomeric microspecies (pH = 7.0, c_BAL = 0.5 mM) L.I. Szekeres, B. Gyurcsik, T. Kiss, Z. Kele, A. Jancsó, "Interaction of Arsenous Acid with the Dithiol-Type Chelator British Anti-Lewisite (BAL): Structure and Stability of Species Formed in an Unexpectedly Complex System”, Inorg. Chem., 57, 7191-7200 (2018).