Factor Xa: Difference between revisions

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====Substrate Recognition Sites ====
====Substrate Recognition Sites ====
<applet load='2PR3' size='300' frame='true' align='right' caption='Structure of factor Xa PBD id: 2PR3' />
The natural substrate of factor Xa is prothromin, which is cleaved after the arginine in the sequence: Ile12-Asp13-Gly14-Arg15-Ile16- Val17-Glu18-Gly19. Arg 15 binds in the S1 pocket, Gly 14 binds the S2 pocket, Ile binds the S4 pocket. The <scene name='Factor_Xa/Transparent_-_no_inhib_-_s1/7'>S1 pocket</scene>, is located next to the catalytic triad, and is formed by loops in residues 214-220 and 189-195 that are linked by a <scene name='Factor_Xa/Transparent_-_no_inhib_-_s1/6'>Cys 220-Cys 191</scene> disulfide bond . Residues 225-228 form the lower portion of the pocket.<ref>Factor X. Wikipedia</ref> The S1 pocket binding selectivity is determined by residues Asp 189, Gly 216, and Gly 226. Asp 189 (R-group pKa: 12.48) most likely forms electrostatic interactions with the S1' Arg 15 (R-group pKa: 4). The <scene name='Factor_Xa/Transparent_-_no_inhib_oxianio/3'>oxyanion hole</scene>  is formed by the backbone amides of Gly193 and Ser195.<ref name="ser wiki">Serine Protease. Wikipedia</ref> The oxyanion hole uses its main chain amide groups to stabilize the tetrahedral intermediate.<ref name="specificity" />
The natural substrate of factor Xa is prothromin, which is cleaved after the arginine in the sequence: Ile12-Asp13-Gly14-Arg15-Ile16- Val17-Glu18-Gly19. Arg 15 binds in the S1 pocket, Gly 14 binds the S2 pocket, Ile binds the S4 pocket. The <scene name='Factor_Xa/Transparent_-_no_inhib_-_s1/7'>S1 pocket</scene>, is located next to the catalytic triad, and is formed by loops in residues 214-220 and 189-195 that are linked by a <scene name='Factor_Xa/Transparent_-_no_inhib_-_s1/6'>Cys 220-Cys 191</scene> disulfide bond . Residues 225-228 form the lower portion of the pocket.<ref>Factor X. Wikipedia</ref> The S1 pocket binding selectivity is determined by residues Asp 189, Gly 216, and Gly 226. Asp 189 (R-group pKa: 12.48) most likely forms electrostatic interactions with the S1' Arg 15 (R-group pKa: 4). The <scene name='Factor_Xa/Transparent_-_no_inhib_oxianio/3'>oxyanion hole</scene>  is formed by the backbone amides of Gly193 and Ser195.<ref name="ser wiki">Serine Protease. Wikipedia</ref> The oxyanion hole uses its main chain amide groups to stabilize the tetrahedral intermediate.<ref name="specificity" />


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====Catalytic Triad====
====Catalytic Triad====
<applet load='2PR3' size='300' frame='true' align='right' caption='Structure of factor Xa PBD id: 2PR3' />
Serine proteases use a His57, Asp102, Ser195 [http://en.wikipedia.org/wiki/Catalytic_triad catalytic triad], each playing an important role. The serine donates an OH group to act as a nucleophile and attack the carbonyl group of the peptide bond that will be broken within the substrate. Histidine coordinates the attack of the peptide bond by accepting the hydrogen from the serine –OH group with a pair of electrons on nitrogen. Aspartate contains a carboxyl group that aids in proper positioning of the histidine and stabilization, through hydrogen bonding.
Serine proteases use a His57, Asp102, Ser195 [http://en.wikipedia.org/wiki/Catalytic_triad catalytic triad], each playing an important role. The serine donates an OH group to act as a nucleophile and attack the carbonyl group of the peptide bond that will be broken within the substrate. Histidine coordinates the attack of the peptide bond by accepting the hydrogen from the serine –OH group with a pair of electrons on nitrogen. Aspartate contains a carboxyl group that aids in proper positioning of the histidine and stabilization, through hydrogen bonding.


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