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001-es BibID:	BIBFORM105430
035-os BibID:	(cikkazonosító)1215 (WoS)000895364600001 (Scopus)85149568475
Első szerző:	Borrego, Jesús
Cím:	Recombinant Expression in Pichia pastoris System of Three Potent Kv1.3 Channel Blockers : Vm24, Anuroctoxin, and Ts6 / Borrego Jesús, Naseem Muhammad Umair, Sehgal Al Nasar Ahmed, Panda Lipsa Rani, Shakeel Kashmala, Gaspar Attila, Nagy Cynthia, Varga Zoltan, Panyi Gyorgy
Dátum:	2022
ISSN:	2309-608X
Megjegyzések:	The Kv1.3 channel has become a therapeutic target for the treatment of various diseases. Several Kv1.3 channel blockers have been characterized from scorpion venom; however, extensive studies require amounts of toxin that cannot be readily obtained directly from venoms. The Pichia pastoris expression system provides a cost-effective approach to overcoming the limitations of chemical synthesis and E. coli recombinant expression. In this work, we developed an efficient system for the production of three potent Kv1.3 channel blockers from different scorpion venoms: Vm24, AnTx, and Ts6. Using the Pichia system, these toxins could be obtained in sufficient quantities (Vm24 1.6 mg/L, AnTx 46 mg/L, and Ts6 7.5 mg/L) to characterize their biological activity. A comparison was made between the activity of tagged and untagged recombinant peptides. Tagged Vm24 and untagged AnTx are nearly equivalent to native toxins in blocking Kv1.3 (Kd = 4.4 pM and Kd = 0.72 nM, respectively), whereas untagged Ts6 exhibits a 53-fold increase in Kd (Kd = 29.1 nM) as compared to the native peptide. The approach described here provides a method that can be optimized for toxin production to develop more selective and effective Kv1.3 blockers with therapeutic potential.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Pichia pastoris recombinant peptides scorpion venoms Kv1.3 blockers
Megjelenés:	Journal of Fungi. - 8 : 11 (2022), p. 1-15. -
További szerzők:	Naseem, Muhammad Umair (1993-) (biofizikus, molekuláris biológus) Sehgal, Al Nasar Ahmed Panda, Lipsa Rani Shakeel, Kashmala Gáspár Attila (1970-) (vegyész, kémikus) Nagy Cynthia (1994-) Varga Zoltán (1969-) (biofizikus, szakfordító) Panyi György (1966-) (biofizikus)
Pályázati támogatás:	K143071 OTKA K127931 OTKA Stipendium Hungaricum Scholarship by the Tempus Public Foundation Egyéb Richter Gedeon Talentum Foundation Egyéb
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001-es BibID:	BIBFORM106364
035-os BibID:	(cikkazonosító)41 (WoS)000916020800001 (Scopus)85146824862
Első szerző:	Naseem, Muhammad Umair (biofizikus, molekuláris biológus)
Cím:	Characterization and Chemical Synthesis of Cm39 (α-KTx 4.8) : a Scorpion Toxin That Inhibits Voltage-Gated K+ Channel KV1.2 and Small- and Intermediate-Conductance Ca2+-Activated K+ Channels KCa2.2 and KCa3.1 / Muhammad Umair Naseem, Georgina Gurrola-Briones, Margarita R. Romero-Imbachi, Jesus Borrego, Edson Carcamo-Noriega, José Beltrán-Vidal, Fernando Z. Zamudio, Kashmala Shakeel, Lourival Domingos Possani, Gyorgy Panyi
Dátum:	2023
ISSN:	2072-6651
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Cm39 scorpion toxin Centruroides margaritatus KV1.2 KCa2.2 KCa3.1 electrophysiology Ca2+-activated channel
Megjelenés:	Toxins. - 15 : 1 (2023), p. 1-21. -
További szerzők:	Gurrola-Briones, Georgina Romero-Imbachi, Margarita R. Borrego, Jesús Carcamo-Noriega, Edson Beltrán-Vidal, José Zamudio, Fernando Z. Shakeel, Kashmala Possani, Lourival Domingos Panyi György (1966-) (biofizikus)
Pályázati támogatás:	K143071 OTKA
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001-es BibID:	BIBFORM116513
035-os BibID:	(Scopus)85173464630 (WOS)001077676500001
Első szerző:	Sanches, Karoline
Cím:	Structure-function relationships in domain peptides : from the sea anemone / Sanches Karoline, Ashwood Lauren M., Olushola-Siedoks Abisola Ave-Maria, Wai Dorothy C. C., Rahman Arfatur, Shakeel Kashmala, Naseem Muhammad Umair, Panyi Gyorgy, Prentis Peter J., Norton Raymond S.
Dátum:	2024
ISSN:	0887-3585
Megjegyzések:	Diverse structural scaffolds have been described in peptides from sea anemones, with the ShKT domain being a common scaffold first identified in ShK toxin from Stichodactyla helianthus. ShK is a potent blocker of voltage-gated potassium channels (KV1.x), and an analog, ShK-186 (dalazatide), has completed Phase 1 clinical trials in plaque psoriasis. The ShKT domain has been found in numerous other species, but only a tiny fraction of ShKT domains has been characterized functionally. Despite adopting the canonical ShK fold, some ShKT peptides from sea anemones inhibit KV1.x, while others do not. Mutagenesis studies have shown that a Lys-Tyr (KY) dyad plays a key role in KV1.x blockade, although a cationic residue followed by a hydrophobic residue may also suffice. Nevertheless, ShKT peptides displaying an ShK-like fold and containing a KY dyad do not necessarily block potassium channels, so additional criteria are needed to determine whether new ShKT peptides might show activity against potassium channels. In this study, we used a combination of NMR and molecular dynamics (MD) simulations to assess the potential activity of a new ShKT peptide. We determined the structure of ShKT-Ts1, from the sea anemone Telmatactis stephensoni, examined its tissue localization, and investigated its activity against a range of ion channels. As ShKT-Ts1 showed no activity against KV1.x channels, we used MD simulations to investigate whether solvent exposure of the dyad residues may be informative in rationalizing and potentially predicting the ability of ShKT peptides to block KV1.x channels. We show that either a buried dyad that does not become exposed during MD simulations, or a partially exposed dyad that becomes buried during MD simulations, correlates with weak or absent activity against KV1.x channels. Therefore, structure determination coupled with MD simulations, may be used to predict whether new sequences belonging to the ShKT family may act as potassium channel blockers.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk molecular dynamics NMR peptide potassium channel sea anemone ShKT domain structure determination
Megjelenés:	Proteins-Structure Function And Bioinformatics. - 92 : 2 (2023), p. 192-205. -
További szerzők:	Ashwood, Lauren M. Olushola-Siedoks, Abisola Ave-Maria Wai, Dorothy C. C. Rahman, Arfatur Shakeel, Kashmala Naseem, Muhammad Umair (1993-) (biofizikus, molekuláris biológus) Panyi György (1966-) (biofizikus) Prentis, Peter Norton, Raymond S.
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001-es BibID:	BIBFORM114858
035-os BibID:	(cikkazonosító)506 (scopus)85168734722 (wos)001056214900001
Első szerző:	Shakeel, Kashmala
Cím:	Of Seven New K⁺ Channel Inhibitor Peptides of Centruroides bonito, α-KTx 2.24 Has a Picomolar Affinity for Kv1.2 / Shakeel Kashmala, Olamendi-Portugal Timoteo, Naseem Muhammad Umair, Becerril Baltazar, Zamudio Fernando Z., Delgado-Prudencio Gustavo, Possani Lourival Domingos, Panyi Gyorgy
Dátum:	2023
ISSN:	2072-6651
Megjegyzések:	Seven new peptides denominated CboK1 to CboK7 were isolated from the venom of the Mexican scorpion Centruroides bonito and their primary structures were determined. The molecular weights ranged between 3760.4 Da and 4357.9 Da, containing 32 to 39 amino acid residues with three putative disulfide bridges. The comparison of amino acid sequences with known potassium scorpion toxins (KTx) and phylogenetic analysis revealed that CboK1 (?-KTx 10.5) and CboK2 (?-KTx 10.6) belong to the ?-KTx 10.x subfamily, whereas CboK3 (?-KTx 2.22), CboK4 (?-KTx 2.23), CboK6 (?-KTx 2.21), and CboK7 (?-KTx 2.24) bear > 95% amino acid similarity with members of the ?-KTx 2.x subfamily, and CboK5 is identical to Ce3 toxin (?-KTx 2.10). Electrophysiological assays demonstrated that except CboK1, all six other peptides blocked the Kv1.2 channel with Kd values in the picomolar range (24?763 pM) and inhibited the Kv1.3 channel with comparatively less potency (Kd values between 20?171 nM). CboK3 and CboK4 inhibited less than 10% and CboK7 inhibited about 42% of Kv1.1 currents at 100 nM concentration. Among all, CboK7 showed out-standing affinity for Kv1.2 (Kd = 24 pM), as well as high selectivity over Kv1.3 (850-fold) and Kv1.1 (~6000-fold). These characteristics of CboK7 may provide a framework for developing tools to treat Kv1.2-related channelopathies.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk CboK Centruroides bonito scorpion toxin Kv1.2 Kv1.3 Kv1.2 channelopathies electrophysiology
Megjelenés:	Toxins. - 15 : 8 (2023), p. 1-20. -
További szerzők:	Olamendi-Portugal, Timoteo Naseem, Muhammad Umair (1993-) (biofizikus, molekuláris biológus) Becerril, Baltazar Zamudio, Fernando Z. Delgado-Prudencio, Gustavo Possani, Lourival Domingos Panyi György (1966-) (biofizikus)
Pályázati támogatás:	K143071 OTKA
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