1ahw
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The tissue factor (TF)-initiated blood coagulation protease cascade can be, greatly inhibited in vivo by a potent anti-human-TF monoclonal antibody, 5G9. This antibody binds the carboxyl module of the extracellular domain, of TF with a nanomolar binding constant and inhibits the formation of the, TF.VIIa.X ternary initiation complex. We have determined the crystal, structures of the extra-cellular modules of human TF, Fab 5G9, and their, complex (TF.5G9) to 2.4 A, 2. 5 A, and 3.0 A, respectively, and measured, the apparent inhibition constants of 5G9 on a panel of TF mutants. In our, unliganded TF structure, a 7 degrees change in the relative orientation, between the D1 and D2 modules was observed when compared with other, published TF structures. Comparison of the free and bound Fab 5G9, ... | + | The tissue factor (TF)-initiated blood coagulation protease cascade can be, greatly inhibited in vivo by a potent anti-human-TF monoclonal antibody, 5G9. This antibody binds the carboxyl module of the extracellular domain, of TF with a nanomolar binding constant and inhibits the formation of the, TF.VIIa.X ternary initiation complex. We have determined the crystal, structures of the extra-cellular modules of human TF, Fab 5G9, and their, complex (TF.5G9) to 2.4 A, 2. 5 A, and 3.0 A, respectively, and measured, the apparent inhibition constants of 5G9 on a panel of TF mutants. In our, unliganded TF structure, a 7 degrees change in the relative orientation, between the D1 and D2 modules was observed when compared with other, published TF structures. Comparison of the free and bound Fab 5G9, indicates that small segmental and side chain variation of the antibody, complementarity determining regions occurred on complexation with TF. The, antibody-antigen recognition involves 18 TF antigen residues and 19 Fab, residues from six CDR with one of the largest buried surface areas seen to, date. A combination of structural and mutagenesis data indicate that, Tyr156, Lys169, Arg200, and Lys201 play the major role in the antibody, recognition. The TF. 5G9 structure provides insights into the mechanism by, which the antibody 5G9 inhibits formation of the TF.VIIa.X ternary, complex. |
==About this Structure== | ==About this Structure== | ||
| - | 1AHW is a | + | 1AHW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Structure known Active Sites: BSC and BSF. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AHW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tissue factor]] | [[Category: tissue factor]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:04:52 2007'' |
Revision as of 11:59, 5 November 2007
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A COMPLEX OF EXTRACELLULAR DOMAIN OF TISSUE FACTOR WITH AN INHIBITORY FAB (5G9)
Overview
The tissue factor (TF)-initiated blood coagulation protease cascade can be, greatly inhibited in vivo by a potent anti-human-TF monoclonal antibody, 5G9. This antibody binds the carboxyl module of the extracellular domain, of TF with a nanomolar binding constant and inhibits the formation of the, TF.VIIa.X ternary initiation complex. We have determined the crystal, structures of the extra-cellular modules of human TF, Fab 5G9, and their, complex (TF.5G9) to 2.4 A, 2. 5 A, and 3.0 A, respectively, and measured, the apparent inhibition constants of 5G9 on a panel of TF mutants. In our, unliganded TF structure, a 7 degrees change in the relative orientation, between the D1 and D2 modules was observed when compared with other, published TF structures. Comparison of the free and bound Fab 5G9, indicates that small segmental and side chain variation of the antibody, complementarity determining regions occurred on complexation with TF. The, antibody-antigen recognition involves 18 TF antigen residues and 19 Fab, residues from six CDR with one of the largest buried surface areas seen to, date. A combination of structural and mutagenesis data indicate that, Tyr156, Lys169, Arg200, and Lys201 play the major role in the antibody, recognition. The TF. 5G9 structure provides insights into the mechanism by, which the antibody 5G9 inhibits formation of the TF.VIIa.X ternary, complex.
About this Structure
1AHW is a Protein complex structure of sequences from Homo sapiens and Mus musculus. Structure known Active Sites: BSC and BSF. Full crystallographic information is available from OCA.
Reference
The mechanism of an inhibitory antibody on TF-initiated blood coagulation revealed by the crystal structures of human tissue factor, Fab 5G9 and TF.G9 complex., Huang M, Syed R, Stura EA, Stone MJ, Stefanko RS, Ruf W, Edgington TS, Wilson IA, J Mol Biol. 1998 Feb 6;275(5):873-94. PMID:9480775
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