A monoclonal antibody which inhibits the factor Va:factor Xa interaction.

Tucker, Marjorie; Foster, W B; Katzmann, JA; Mann, Kenneth G.

doi:10.1016/s0021-9258(18)33180-6

Cited by 48 publications

(12 citation statements)

References 21 publications

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“…specific for the heavy chain of bovine factor Va (Foster et al, 1983a;Tucker et al, 1983), identical results are obtained.…”

Section: Resultssupporting

confidence: 65%

“…These data do not shed light upon the specific interaction within the prothrombinase complex inhibited by these anti-factor Va antibodies (i.e., factor Va-membrane interaction, factor Vafactor Xa interaction, or factor Va-prothrombin association). However, it has been previously established that aBFV-4 is directed against the light chain of the cofactor and inhibits the interaction between factor Va and membrane-bound factor Xa (Tucker et al, 1983).…”

Section: Resultsmentioning

confidence: 99%

“…Earlier data using light fluorescence polarization measurements and gel exclusion chromatography showed that monoclonal antibody aBFV-4 which recognizes factor V au: inhibits factor Va interaction with factor Xa (Tucker et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

“…The nomenclature given in the present paper is different from that used previously. For comparison, the antibodies are identical as follows: aBFV-1, previous designations IB6 and a[D (Foster et al, 1982;Tucker et al, 1983); aBFV-4, previous designations IIC3 and ajE (Foster etal., 1982(Foster etal., ,1983aTucker et al, 1983);aBFV-5, previous designation IIIA5 (Foster et al, 1982). Purified aBFV-4 and aBFV-5 immunoglobins (IgGs) were immobilized on CNBr-activated Sepharose CL-4B as described (March et al, 1974).…”

Section: Methodsmentioning

confidence: 99%

“…The factor Xa binding site for factor Va is independent of the NFU-termirtal portion of XaLc (Skogen et al, 1984;Morita & Jackson, 1986;Persson et al, 1993) and has been suggested to involve residues 263-274 of factor Xanc (Chattopadhyay etal., 1992). The factor Va binding site for factor Xa involves Ca2+ and both chains of the cofactor (Tucker et al, 1983;Guinto & Esmon, 1984;Annamalai et al, 1987;Pryzdial & Mann, 1991). Each chain has been shown to independently interact with rx-EGR-Xa (Pryzdial & Mann, 1991).…”

mentioning

confidence: 99%

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Contribution of the Heavy and Light Chains of Factor Va to the Interaction with Factor Xa

Kalafatis¹,

Xue²,

Lawler³

et al. 1994

Biochemistry

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The interactions of the isolated heavy and light chains of factor Va with factor Xa were evaluated using active-site-modified factor Xa [(carboxytetramethyl)rhodamine-Glu-Gly- Arg-factor Xa (ctr-EGR-Xa)]. The Kd for the factor Va heavy-chain interaction with ctr-EGR-Xa was 60 microM. A series of monoclonal antibodies directed against bovine factor Va were tested for their ability to inhibit thrombin formation in an assay using the fluorescent thrombin inhibitor dansylarginine N,N-(3-ethyl-1,5-pentanediyl)amide (DAPA). Monoclonal antibody alpha BFV-4, which recognizes the light chain of the cofactor, was found to inhibit the formation of thrombin. Similarly, monoclonal antibody alpha BFV-5, which is directed against the heavy chain of the cofactor, was found to inhibit thrombin formation. In contrast, monoclonal antibody alpha BFV-1, also directed against the heavy chain of the cofactor, did not inhibit thrombin generation by the prothrombinase complex. Monoclonal antibodies alpha BFV-4 and alpha BFV-5 inhibited the interaction of active-site-modified radiolabeled factor Xa (125I-Xa-EGR) with factor Va bound to PC/PS-coated microtiter wells, whereas nonimmune mouse IgG did not have any effect on the 125I-Xa-EGR.membrane-bound factor Va interaction. The antibodies effect upon the phospholipid-independent interaction between the cofactor and ctr-EGR-Xa was evaluated by analytical ultracentrifugation. Both alpha BFV-4 and alpha BFV-5 inhibited the phospholipid-independent interaction between factor Va and ctr-EGR-Xa.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…specific for the heavy chain of bovine factor Va (Foster et al, 1983a;Tucker et al, 1983), identical results are obtained.…”

Section: Resultssupporting

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Contribution of the Heavy and Light Chains of Factor Va to the Interaction with Factor Xa

Kalafatis¹,

Xue²,

Lawler³

et al. 1994

Biochemistry

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Monoclonal antibodies in the study of structure‐function relationships of proteins

Cotton

1985

Medicinal Research Reviews

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Binding sites for blood coagulation factor Xa and protein S involving residues 493–506 in factor Va

et al. 1996

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Inactivation due to cleavage of Factor Va (FVa) at Arg 506 by activated protein C (APC) helps to downregulate blood coagulation. To identify potential functional roles of amino acids near Arg 506, synthetic overlapping pentadecapeptides comprising FVa heavy chain residues 481-525 were tested for their ability to inhibit prothrombin activation by prothrombinase complexes [Factor Xa (FXa):FVa:phospholipids:Ca2+]. The most potent inhibition was observed for peptide VP493 (residues 493-506), with 50% inhibition at 2.5 pM. VP493 also inhibited FXa in plasma in FXa-1-stage clotting assays by 50% at 3 pM. When the C-terminal carboxamide group of VP493 was replaced by a carboxyl group, most prothrombinase inhibitory activity was lost. VP493 preincubated with FXa inhibited prothrombinase with a pattern of mixed inhibition. Homologous peptides from Factor VI11 sequences did not inhibit prothrombinase. Affinity-purified antibodies to VP493 inhibited prothrombinase activity and prolonged FXa-I-stage clotting times. VP493 also blocked the ability of protein S to inhibit prothrombinase independently of APC. Immobilized VP493 bound specifically with similar affinity to both FXa and protein S (Kd -40 nM), but did not measurably bind prothrombin or APC. These studies suggest that FVa residues 493-506 contribute to binding sites for both FXa and protein S, providing a rationale for the ability of protein S to negate the protective effect of FXa toward APC cleavage of FVa. Possible loss of this FVa binding site for FXa due to cleavage at Arg 506 by APC may help explain why this cleavage causes 40% decrease in FVa activity and facilitates inactivation of FVa.

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A monoclonal antibody which inhibits the factor Va:factor Xa interaction.

Cited by 48 publications

References 21 publications

Contribution of the Heavy and Light Chains of Factor Va to the Interaction with Factor Xa

Contribution of the Heavy and Light Chains of Factor Va to the Interaction with Factor Xa

Monoclonal antibodies in the study of structure‐function relationships of proteins

Binding sites for blood coagulation factor Xa and protein S involving residues 493–506 in factor Va

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