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001-es BibID:	BIBFORM093898
035-os BibID:	(cikkazonosító)544 (WoS)000642809000001 (Scopus)85103814901
Első szerző:	Gindele Réka (molekuláris biológus)
Cím:	Investigation of the Differences in Antithrombin to Heparin Binding among Antithrombin Budapest 3, Basel, and Padua Mutations by Biochemical and In Silico Methods / Gindele Réka, Pénzes-Daku Krisztina, Balogh Gábor, Kállai Judit, Bogáti Réka, Bécsi Bálint, Erdődi Ferenc, Katona Éva, Bereczky Zsuzsanna
Dátum:	2021
ISSN:	2218-273X
Megjegyzések:	Antithrombin (AT) is a serine protease inhibitor, its activity is highly accelerated by heparin. Mutations at the heparin-binding region lead to functional defect, type II heparin-binding site (IIHBS) AT deficiency. The aim of this study was to investigate and compare the molecular background of AT Budapest 3 (p.Leu131Phe, ATBp3), AT Basel (p.Pro73Leu), and AT Padua (p.Arg79His) mutations. Advanced in silico methods and heparin-binding studies of recombinant AT proteins using surface plasmon resonance method were used. Crossed immunoelectrophoresis and Differential Scanning Fluorimetry (NanoDSF) were performed in plasma samples. Heparin affinity of AT Padua was the lowest (KD = 1.08 x 10(-6) M) and had the most severe consequences affecting the allosteric pathways of activation, moreover significant destabilizing effects on AT were also observed. KD values for AT Basel, ATBp3 and wild-type AT were 7.64 x 10(-7) M, 2.15 x 10(-8) M and 6.4 x 10(-10) M, respectively. Heparin-binding of AT Basel was slower, however once the complex was formed the mutation had only minor effect on the secondary and tertiary structures. Allosteric activation of ATBp3 was altered, moreover decreased thermostability in ATBp3 homozygous plasma and increased fluctuations in multiple regions of ATBp3 were observed by in silico methods suggesting the presence of a quantitative component in the pathogenicity of this mutation due to molecular instability.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Biomolecules. - 11 : 4 (2021), p. 1-18. -
További szerzők:	Pénzes-Daku Krisztina (1978-) (biológus) Balogh Gábor (1991-) (gyógyszerész) Kállai Judit (1983-) (molekuláris biológus) Kissné Bogáti Réka (1988-) (tudományos segédmunkatárs) Bécsi Bálint (1981-) (vegyészmérnök) Erdődi Ferenc (1953-) (biokémikus) Katona Éva (1961-) (klinikai biokémikus) Bereczky Zsuzsanna (1974-) (orvosi laboratóriumi diagnosztika szakorvos)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00039 GINOP GINOP-2.3.2-15-2016-00044 GINOP GINOP-2.3.3-15-2016-00020 GINOP
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM120395
035-os BibID:	(Scopus)85187431460
Első szerző:	Kállai Judit (molekuláris biológus)
Cím:	Clinical and Molecular Characterization of Nine Novel Antithrombin Mutations / Judit Kállai, Réka Gindele, Krisztina Pénzes-Daku, Gábor Balogh, Réka Bogáti, Bálint Bécsi, Éva Katona, Zsolt Oláh, Péter Ilonczai, Zoltán Boda, Ágnes Róna-Tas, László Nemes, Imelda Marton, Zsuzsanna Bereczky
Dátum:	2024
ISSN:	1422-0067
Megjegyzések:	Antithrombin (AT) is the major plasma inhibitor of thrombin (FIIa) and activated factor X (FXa), and antithrombin deficiency (ATD) is one of the most severe thrombophilic disorders. In this study, we identified nine novel AT mutations and investigated their genotype?phenotype correlations. Clinical and laboratory data from patients were collected, and the nine mutant AT proteins (p.Arg14Lys, p.Cys32Tyr, p.Arg78Gly, p.Met121Arg, p.Leu245Pro, p.Leu270Argfs14, p.Asn450Ile, p.Gly456delins_Ala_Thr and p.Pro461Thr) were expressed in HEK293 cells; then,Western blotting, N-Glycosidase F digestion, and ELISA were used to detect wild-type and mutant AT. RT-qPCR was performed to determine the expression of AT mRNA from the transfected cells. Functional studies (AT activity in the presence and in the absence of heparin and heparin-binding studies with the surface plasmon resonance method) were carried out. Mutations were also investigated by in silico methods. Type I ATD caused by altered protein synthesis (p.Cys32Tyr, p.Leu270Argfs14, p.Asn450Ile) or secretion disorder (p.Met121Arg, p.Leu245Pro, p.Gly456delins_Ala_Thr) was proved in six mutants, while type II heparin-binding-site ATD (p.Arg78Gly) and pleiotropic-effect ATD (p.Pro461Thr) were suggested in two mutants. Finally, the pathogenic role of p.Arg14Lys was equivocal. We provided evidence to understand the pathogenic nature of novel SERPINC1 mutations through in vitro expression studies.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk antithrombin antithrombin deficiency SERPINC1 mutation expression study surface plasmon resonance in silico methods
Megjelenés:	International Journal Of Molecular Sciences. - 25 : 5 (2024), p. 1-19.
További szerzők:	Gindele Réka (1987-) (molekuláris biológus) Pénzes-Daku Krisztina (1978-) (biológus) Balogh Gábor Kissné Bogáti Réka (1988-) (tudományos segédmunkatárs) Bécsi Bálint (1981-) (vegyészmérnök) Katona Éva (1986-) (molekuláris biológus) Oláh Zsolt (1974-) (belgyógyász) Ilonczai Péter (1977-) (orvos, belgyógyász, haematológus szakorvos) Boda Zoltán (1947-) (belgyógyász, haematologus, klinikai onkológus) Róna-Tas Ágnes Nemes László Marton Imelda Bereczky Zsuzsanna (1974-) (orvosi laboratóriumi diagnosztika szakorvos)
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