Factor Xa: Difference between revisions
Michal Harel (talk | contribs) No edit summary |
Michal Harel (talk | contribs) No edit summary |
||
| Line 53: | Line 53: | ||
==Post-Translational Modifications== | ==Post-Translational Modifications== | ||
Factor X is cleaved by factor IXa (in the intrinsic pathway), or by factor VIIa (in the extrinsic pathway) to release the activation peptide, and yield the active factor Xa. The vitamin K-dependent, enzymatic carboxylation of some glutamate residues allows the modified protein to bind calcium via the GLA domain. Zymogen human factor X has four carbohydrate-attachment sites in the activation peptide, O-glycosidic linkages are to Thr17 and Thr29, and N-glycosidic linkages are to Asn39 and Asn49. | Factor X is cleaved by factor IXa (in the intrinsic pathway), or by factor VIIa (in the extrinsic pathway) to release the activation peptide, and yield the active factor Xa. The vitamin K-dependent, enzymatic carboxylation of some glutamate residues allows the modified protein to bind calcium via the GLA domain. Zymogen human factor X has four carbohydrate-attachment sites in the activation peptide, O-glycosidic linkages are to Thr17 and Thr29, and N-glycosidic linkages are to Asn39 and Asn49. | ||
==Enzyme Mechanism== | ==Enzyme Mechanism== | ||
| Line 70: | Line 69: | ||
A more recent crystal structure of α-Lytic protease, published in 2006 with 0.82 Å resolution argues against both the his flip mechanism and the presence of a LBHB between His57 and Asp102 (2.755 Å in this structure). Fuhrmann ''et al'' suggests that a LBHB may have been present in the subtilisin strucutre, it is not required for the serine protease mechanism. Instead they state that the chymotrypsin-like proteases may use a network of optimized hydrogen bonds to position the stabilize the tetrahedral intermediate and position the catalytic triad. Ser195 undergoes a shift of ~1Å upon protonation of His57 that destabilizes the His57-Ser195 H-bond. This conformation change would prevent His57 from reprotonating Ser195 leading to regeneration of the substrate.<ref name="subang" /> | A more recent crystal structure of α-Lytic protease, published in 2006 with 0.82 Å resolution argues against both the his flip mechanism and the presence of a LBHB between His57 and Asp102 (2.755 Å in this structure). Fuhrmann ''et al'' suggests that a LBHB may have been present in the subtilisin strucutre, it is not required for the serine protease mechanism. Instead they state that the chymotrypsin-like proteases may use a network of optimized hydrogen bonds to position the stabilize the tetrahedral intermediate and position the catalytic triad. Ser195 undergoes a shift of ~1Å upon protonation of His57 that destabilizes the His57-Ser195 H-bond. This conformation change would prevent His57 from reprotonating Ser195 leading to regeneration of the substrate.<ref name="subang" /> | ||
</StructureSection> | |||
==3D structures of factor Xa== | ==3D structures of factor Xa== | ||