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001-es BibID:	BIBFORM010451
Első szerző:	Pénzes-Daku Krisztina (biológus)
Cím:	Molecular mechanism of the interaction between activated factor XIII and its glutamine donor peptide substrate / K. Pénzes, K. E. Kövér, F. Fazakas, G. Haramura, L. Muszbek
Dátum:	2009
ISSN:	1538-7933 (Print)
Megjegyzések:	Activated factor XIII (FXIII), a dimer of truncated A-subunits (FXIII-A2), is a transglutaminase that crosslinks primary amines to peptide-bound glutamine residues. Because in the few natural substrates of FXIII-A2 no consensus sequence could be identified around the reactive glutamine, studying the interaction between individual substrates and FXIII-A2* is of primary importance. Most of the alpha2-plasmin inhibitor (alpha2PI) molecules become truncated by a plasma protease, and the truncated isoform (N1-alpha2PI) is an important substrate of FXIII-A2. The crosslinking of N1-alpha2PI to fibrin plays a major role in protecting fibrin from fibrinolysis. METHODS: We studied the interaction of FXIII-A2 with its dodecapeptide glutamine donor substrate, N1-alpha2PI(1-12), the sequence of which corresponds to the N-terminal sequence of N1-alpha2PI. Kinetic parameters for N1-alpha2PI(1-12) and for its truncated or synthetic mutants were determined by a spectrophotometric assay. The interaction of N1-alpha2PI(1-12) with FXIII-A2* was investigated by proton nuclear magnetic resonance (NMR) and saturating transfer difference (STD) NMR. RESULTS AND CONCLUSIONS: Kinetic experiments with peptides in which the Asn1 residue was either truncated or replaced by alanine and proton NMR analysis of the FXIII-A2-N1-alpha2PI(1-12) complex demonstrated that Asn1 is essential for effective enzyme-substrate interaction. Experiments with C-terminally truncated peptides proved that amino acids 7-12 are essential for the interaction of N1-alpha2PI(1-12) with the enzyme, and suggested the existence of a secondary binding site on FXIII-A2. Hydrophobic residues, particularly Leu10 and the C-terminal Lys12, seemed to be especially important in this respect, and direct interaction between hydrophobic C-terminal residues and FXIII-A2* was demonstrated by STD NMR.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban Amino Acid Sequence Animals Asparagine Binding Sites Cattle Factor XIII
Megjelenés:	Journal of Thrombosis and Haemostasis. - 7 : 4 (2009), p. 627-633. -
További szerzők:	Kövér Katalin, E. (1956-2023) (vegyész) Fazakas Ferenc (1969-) (molekuláris biológus) Haramura Gizella (1957-) (vezető analitikus) Muszbek László (1942-) (haematológus, kutató orvos)
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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