FIXa regions mediating the interaction with FVIIIa
| FIXa domain or region . | Residues . | FVIIIa counterpart . | Experimental strategy and references . | ||
|---|---|---|---|---|---|
| Legacy∗ numbering . | Chymotrypsinogen† numbering . | Domain . | Legacy numbering . | ||
| Gla‡ | Y1-S3 E21-F25 V46-D47 | n.a. | C2 | E2228-V2240 | Gla peptides41 rFVIII domains/peptides43 Small-angle X-ray scattering33 |
| Gla§ | N34-D47 | n.a. | C1 | S2113-N2118 | Computational docking and MD simulations32 |
| EGF1§ | N67, S68 E78, and K80 | n.a. | A3 | T1695, H1697 T1739, and Q1745-Y1748 | Computational docking and MD simulations32 |
| EGF2 | T87-D104 | n.a. | A3 | Q1692-H1697 N1770-M1772 E1793-Q1798 T1811-K1818 | rFIX variants38,42 rFVIII variants44,46 Computational docking and MD simulations32 |
| Protease, 99c-loop | Y259-Y266 | Y94-Y99 | A3 | I1790-Q1798 R1803-K1818 | rFVIII variants44,46 Small-angle X-ray scattering33 |
| Protease, exosite II | K293-K301 | K126-K132 | A2, A3 | R698, K707-N714 E1793, Q1796 | rFVIII variants45,46 HDX-MS of rFIX variants27 Computational docking and MD simulations32 |
| Protease, exosite II | L330-R338 | L162-R170 | A2 | S558-M567 | rFIX variants; rFVIII domains/peptides39 HDX-MS of rFIX variants27 Computational docking and MD simulations32 |
| Protease, exosite II | N406-E410 | N236-E240 | a2 | E738 | HDX-MS of rFIX variants27 Computational docking and MD simulations32 |
| FIXa domain or region . | Residues . | FVIIIa counterpart . | Experimental strategy and references . | ||
|---|---|---|---|---|---|
| Legacy∗ numbering . | Chymotrypsinogen† numbering . | Domain . | Legacy numbering . | ||
| Gla‡ | Y1-S3 E21-F25 V46-D47 | n.a. | C2 | E2228-V2240 | Gla peptides41 rFVIII domains/peptides43 Small-angle X-ray scattering33 |
| Gla§ | N34-D47 | n.a. | C1 | S2113-N2118 | Computational docking and MD simulations32 |
| EGF1§ | N67, S68 E78, and K80 | n.a. | A3 | T1695, H1697 T1739, and Q1745-Y1748 | Computational docking and MD simulations32 |
| EGF2 | T87-D104 | n.a. | A3 | Q1692-H1697 N1770-M1772 E1793-Q1798 T1811-K1818 | rFIX variants38,42 rFVIII variants44,46 Computational docking and MD simulations32 |
| Protease, 99c-loop | Y259-Y266 | Y94-Y99 | A3 | I1790-Q1798 R1803-K1818 | rFVIII variants44,46 Small-angle X-ray scattering33 |
| Protease, exosite II | K293-K301 | K126-K132 | A2, A3 | R698, K707-N714 E1793, Q1796 | rFVIII variants45,46 HDX-MS of rFIX variants27 Computational docking and MD simulations32 |
| Protease, exosite II | L330-R338 | L162-R170 | A2 | S558-M567 | rFIX variants; rFVIII domains/peptides39 HDX-MS of rFIX variants27 Computational docking and MD simulations32 |
| Protease, exosite II | N406-E410 | N236-E240 | a2 | E738 | HDX-MS of rFIX variants27 Computational docking and MD simulations32 |
HDX-MS, hydrogen-deuterium exchange-mass spectrometry; MD, molecular dynamics; n.a., not applicable; r, recombinant.
Legacy numbering represents mature FIX with residue 1 corresponding to the first residue of the Gla domain (which equals residue 47 in the numbering format of the Human Genome Variation Society).132
Chymotrypsinogen numbering of the serine protease domain, as originally described by Bode et al13
FIXa-FVIIIa model in which the Gla domain is assumed to interact with the C2 domain of FVIIIa.
FIXa-FVIIIa model in which the Gla domain is assumed to interact with the C1 domain of FVIIIa.