User:Cody Couperus/Sandbox 1: Difference between revisions

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==Prothrombin Activation==

[[Image:Prothrombin activation ~~scheme_2~~.png|300px|right|thumb| Activation scheme of in vivo activation of prothrombin by the prothrombinase complex in presence of calcium and a phospholipid bilayer]]

[[Image:Prothrombin activation scheme_3.png|300px|right|thumb| Activation scheme of in vivo activation of prothrombin by the prothrombinase complex in presence of calcium and a phospholipid bilayer]]

[[Image:Prothrombin activation ~~scheme_nofva~~.png|300px|right|thumb| Activation scheme of in vivo activation of prothrombin by FXa in the absence of FVa.]]

[[Image:Prothrombin activation scheme_nofva3.png|300px|right|thumb| Activation scheme of in vivo activation of prothrombin by FXa in the absence of FVa.]]

Prothrombin is the zymogen form of thrombin. From N-terminal to C-terminal it consists of a Gla domain, two kringle domains, and a catalytic domain.

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The <scene name='58/583418/A_chain_nospin/1' target='0'>A chain</scene> is mostly helical and is wound around the B chain and shaped like a boomerang. It is bound to the B chain mostly through side chain interactions including a salt bridge and a hydrogen bond cluster at residues D14, E8, and E14c.<ref name='eight'/> Furthermore the C-terminus region forms a short amphipathic helix with hydrophobic side chains interacting with the B chain.<ref name='eight'/>

The <scene name='58/583418/B_chain/1~~' target='0~~'>B chain</scene> contains the active site of the protein and has numerous notable structural features. The active site is formed at the rims of two interacting 6 stranded <scene name='58/583418/Beta_barrel/2'>beta barrel domains</scene>(N-terminal barrel in red and C-terminal barrel in orange) which are surrounded by 4 helical regions and many turns.

The <scene name='58/583418/B_chain/1'>B chain</scene> contains the active site of the protein and has numerous notable structural features. The active site is formed at the rims of two interacting 6 stranded <scene name='58/583418/Beta_barrel/2'>beta barrel domains</scene>(N-terminal barrel in red and C-terminal barrel in orange) which are surrounded by 4 helical regions and many turns.

The serine protease <scene name='58/583418/Catalytic_triad/1'>catalytic triad</scene>[http://en.wikipedia.org/wiki/Catalytic_triad wiki] residues, based on chymotrypsin numbering, are Ser195, His57, and Asp102. As is common with serine proteases, an <scene name='58/583418/Oxyanion_hole/2'>oxyanion hole</scene> hole is formed by backbone amides of Ser195 and Gly193.<ref name='seven'/> This has the functional role of stabilizing the oxyanion intermediate involved in the serine protease mechanism by hydrogen bonding to the oxygen of the P1 residue (standard substrate-protease nomeclature <ref>PMID: 22925665</ref>. In addition, since thrombin cleaves after Arg/Lys the <scene name='58/583418/S1/2'>S1 specificity site</scene>, formed by the 180s- and 220s- loops, has Asp189 at the base to form a salt bridge with the incoming substrate. Furthermore, the S4 binding pocket accommodates hydrophobic substrate residues.

@@ Line 35: / Line 35: @@
 ==Prothrombin Activation==
-[[Image:Prothrombin activation scheme_2.png|300px|right|thumb| Activation scheme of in vivo activation of prothrombin by the prothrombinase complex in presence of calcium and a phospholipid bilayer]]
+[[Image:Prothrombin activation scheme_3.png|300px|right|thumb| Activation scheme of in vivo activation of prothrombin by the prothrombinase complex in presence of calcium and a phospholipid bilayer]]
-[[Image:Prothrombin activation scheme_nofva.png|300px|right|thumb| Activation scheme of in vivo activation of prothrombin by FXa in the absence of FVa.]]
+[[Image:Prothrombin activation scheme_nofva3.png|300px|right|thumb| Activation scheme of in vivo activation of prothrombin by FXa in the absence of FVa.]]
 Prothrombin is the zymogen form of thrombin. From N-terminal to C-terminal it consists of a Gla domain, two kringle domains, and a catalytic domain.
@@ Line 55: / Line 55: @@
 The <scene name='58/583418/A_chain_nospin/1' target='0'>A chain</scene> is mostly helical and is wound around the B chain and shaped like a boomerang. It is bound to the B chain mostly through side chain interactions including a salt bridge and a hydrogen bond cluster at residues D14, E8, and E14c.<ref name='eight'/> Furthermore the C-terminus region forms a short amphipathic helix with hydrophobic side chains interacting with the B chain.<ref name='eight'/>
-The <scene name='58/583418/B_chain/1' target='0'>B chain</scene> contains the active site of the protein and has numerous notable structural features. The active site is formed at the rims of two interacting 6 stranded <scene name='58/583418/Beta_barrel/2'>beta barrel domains</scene>(N-terminal barrel in red and C-terminal barrel in orange) which are surrounded by 4 helical regions and many turns.
+The <scene name='58/583418/B_chain/1'>B chain</scene> contains the active site of the protein and has numerous notable structural features. The active site is formed at the rims of two interacting 6 stranded <scene name='58/583418/Beta_barrel/2'>beta barrel domains</scene>(N-terminal barrel in red and C-terminal barrel in orange) which are surrounded by 4 helical regions and many turns.
 The serine protease <scene name='58/583418/Catalytic_triad/1'>catalytic triad</scene>[http://en.wikipedia.org/wiki/Catalytic_triad wiki] residues, based on chymotrypsin numbering, are Ser195, His57, and Asp102. As is common with serine proteases, an <scene name='58/583418/Oxyanion_hole/2'>oxyanion hole</scene> hole is formed by backbone amides of Ser195 and Gly193.<ref name='seven'/> This has the functional role of stabilizing the oxyanion intermediate involved in the serine protease mechanism by hydrogen bonding to the oxygen of the P1 residue (standard substrate-protease nomeclature <ref>PMID: 22925665</ref>. In addition, since thrombin cleaves after Arg/Lys the <scene name='58/583418/S1/2'>S1 specificity site</scene>, formed by the 180s- and 220s- loops, has Asp189 at the base to form a salt bridge with the incoming substrate. Furthermore, the S4 binding pocket accommodates hydrophobic substrate residues.