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Titolo:
Protease and EGF1 domains of factor IXa play distinct roles in binding to factor VIIIa - Importance of helix 330 (helix 162 in chymotrypsin) of protease domain of factor IXa in its interaction with factor VIIIa
Autore:
Mathus, A; Bajaj, SP;
Indirizzi:
St Louis Univ, Hlth Sci Ctr, Sch Med, Dept Med, St Louis, MO 63110 USA St Louis Univ St Louis MO USA 63110 Med, Dept Med, St Louis, MO 63110 USA St Louis Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA St Louis UnivSt Louis MO USA 63110 , Dept Pathol, St Louis, MO 63110 USA St Louis Univ, Sch Med, Dept Biochem, St Louis, MO 63110 USA St Louis Univ St Louis MO USA 63110 Dept Biochem, St Louis, MO 63110 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 26, volume: 274, anno: 1999,
pagine: 18477 - 18486
SICI:
0021-9258(19990625)274:26<18477:PAEDOF>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
COAGULATION FACTOR-IX; GAMMA-CARBOXYGLUTAMIC ACID; AFFINITY CA2+-BINDING SITE; FACTOR-X ACTIVATION; BLOOD-COAGULATION; HEMOPHILIA-B; TISSUE FACTOR; ACTIVE-SITE; NUCLEOTIDE-SEQUENCE; CATALYTIC ACTIVITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Bajaj, SP St,POBis Univ, Hlth Sci Ctr, Sch Med, Dept Med, 3635 Vista Ave &Grand Blvd St Louis Univ 3635 Vista Ave & Grand Blvd,POB 15250 St Louis MOUSA 63110
Citazione:
A. Mathus e S.P. Bajaj, "Protease and EGF1 domains of factor IXa play distinct roles in binding to factor VIIIa - Importance of helix 330 (helix 162 in chymotrypsin) of protease domain of factor IXa in its interaction with factor VIIIa", J BIOL CHEM, 274(26), 1999, pp. 18477-18486

Abstract

Previous studies revealed that cleavage at Arg-318-Ser-319 in the proteasedomain autolysis loop of factor Ma results in its diminished binding to factor VIIIa. Now, we have investigated the importance of adjacent surface-exposed helix 330-338 (162-170 in chymotrypsin numbering) of IX in its interaction with VIIIa, IXWT, eight point mutants mostly based on hemophilia B patients, and a replacement mutant (IXhelixVII in which helix 330-338 is replaced by that of factor VII) were expressed, purified, and characterized. Each mutant was activated normally by VIIa-tissue factor-Ca2+ or XIa-Ca2+, However, in both the presence and absence of phospholipid, interaction of each activated mutant with VIIIa was impaired. The role of IX EGF1 domain in binding to VIIIa was also examined, Two mutants (IXQ50P and IXPCEGF1, in which EGF1 domain is replaced by that of protein C) were used. Strikingly, interactions of the activated EGF1 mutants with VIIIa were impaired only in the presence of phospholipid. We conclude that helix 330 in Ma provides a critical binding site for VIIIa and that the EGF1 domain in this context primarily serves to correctly position the protease domain above the phospholipid surface for optimal interaction with VIIIa.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 08:48:58