Factor Xa: Difference between revisions
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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. Arg15 binds in the S1 pocket, Gly14 binds the S2 pocket. Ile binds the S4 pocket. The <scene name='Factor_Xa/Transparent_-_no_inhib_-_s1/3'>S1 pocket</scene> determines binding selectivity for factor Xa and is formed by loops in residues 214-220 and 189-195 that are linked by a Cys220-Cys191 disulfide bond. Residues 225-228 form the lower portion of the pocket.<ref>Factor X. Wikipedia</ref> The <scene name='Factor_Xa/Transparent_-_no_inhib_-oxy_ho/1'>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. Arg15 binds in the S1 pocket, Gly14 binds the S2 pocket. Ile binds the S4 pocket. The <scene name='Factor_Xa/Transparent_-_no_inhib_-_s1/3'>S1 pocket</scene> determines binding selectivity for factor Xa and is formed by loops in residues 214-220 and 189-195 that are linked by a Cys220-Cys191 disulfide bond. Residues 225-228 form the lower portion of the pocket.<ref>Factor X. Wikipedia</ref> The <scene name='Factor_Xa/Transparent_-_no_inhib_-oxy_ho/1'>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 <scene name='Factor_Xa/Transparent_-_no_inhib_-_s2/ | The <scene name='Factor_Xa/Transparent_-_no_inhib_-_s2/3'>S2 site</scene> of factor Xa is formed by the 90s loop which is positioned adjacent to His57. Consistent with glycine as the P2 element in prothrombin, S2 is a small, shallow pocket.<ref name="Inhib">PMID: 11172669</ref> | ||
<scene name='Factor_Xa/Transparent_-_no_inhib_s4/1'>S4 pocket</scene> is formed between the 90s and 170s loops and binds an Ile. This region contains 3 ligand binding domains. The <scene name='Factor_Xa/Transparent_-_no_inhib_phob_bo/3'>hydrophobic box</scene> is located at the entrance to S4 and contains Phe174, Tyr99 and Trp215, which form a deep aryl-binding pocket. The <scene name='Factor_Xa/Transparent_-_no_inhib_oxianio/2'>cationic hole</scene> is formed by the backbone carbonyl and side chain of Glu97 and the backbone carbonyl of Lys96. The <scene name='Factor_Xa/Transparent_-_no_inhib-_h2o_si/2'>water site</scene> is composed of the hydrophobic side chains of Thr98, Ile175 and Thr177 and traps a water molecule. <ref name="Inhib" /> | <scene name='Factor_Xa/Transparent_-_no_inhib_s4/1'>S4 pocket</scene> is formed between the 90s and 170s loops and binds an Ile. This region contains 3 ligand binding domains. The <scene name='Factor_Xa/Transparent_-_no_inhib_phob_bo/3'>hydrophobic box</scene> is located at the entrance to S4 and contains Phe174, Tyr99 and Trp215, which form a deep aryl-binding pocket. The <scene name='Factor_Xa/Transparent_-_no_inhib_oxianio/2'>cationic hole</scene> is formed by the backbone carbonyl and side chain of Glu97 and the backbone carbonyl of Lys96. The <scene name='Factor_Xa/Transparent_-_no_inhib-_h2o_si/2'>water site</scene> is composed of the hydrophobic side chains of Thr98, Ile175 and Thr177 and traps a water molecule. <ref name="Inhib" /> | ||
