Thrombin: Difference between revisions
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By balancing substrate specificity, activity, and inhibition thrombin plays a central role in the blood coagulation cascade. <ref name="three"/> | By balancing substrate specificity, activity, and inhibition thrombin plays a central role in the blood coagulation cascade. <ref name="three"/> | ||
[[Image:Substrates.png|300px|center|thumb| Coagulation related substrates of thrombin, excluding serpin inhibitors.]] | [[Image:Substrates.png|300px|center|thumb| Coagulation related substrates of thrombin, excluding serpin inhibitors.]] | ||
==The Thrombin Life Cycle== | ==The Thrombin Life Cycle== | ||
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The <scene name='58/583418/Sodium_binding_loop/1'>sodium binding site</scene> is formed by the 180s- and 220s- loops. Na+ is bound by the backbone oxygens of Arg221a and Lys224 in addition to four water molecules in a classic [http://chemwiki.ucdavis.edu/Inorganic_Chemistry/Crystal_Field_Theory/High_Spin_and_Low_Spin_Complexes#Octahedral_Geometry octahedral geometry]<ref>PMID: 9108691</ref>. Through the covelent disulfide linkage between Cys220 and Cys 191 the sodium binding site is linked to Ser195 and the oxyanion hole. | The <scene name='58/583418/Sodium_binding_loop/1'>sodium binding site</scene> is formed by the 180s- and 220s- loops. Na+ is bound by the backbone oxygens of Arg221a and Lys224 in addition to four water molecules in a classic [http://chemwiki.ucdavis.edu/Inorganic_Chemistry/Crystal_Field_Theory/High_Spin_and_Low_Spin_Complexes#Octahedral_Geometry octahedral geometry]<ref>PMID: 9108691</ref>. Through the covelent disulfide linkage between Cys220 and Cys 191 the sodium binding site is linked to Ser195 and the oxyanion hole. | ||
'''Thrombin''' is a "trypsin-like" serine protease. Its structure (PDB code [[1ppb]]) is shown here with a peptide chloroketone inhibitor (PPACK). The thrombin A chain (cleaved N terminal fragement) is shown in cyan and the B chain is shown in red. The <scene name='Serine_Protease/Active_site/2'>Active site</scene> is made up of a catalytic triad of Ser195, His57 and Asp102, backed up by Ser214. The peptide chloroketone inhibitor (PPACK) is shown in purple. A closeup shows the <scene name='Serine_Protease/Activation_site/2'>activation site</scene> at which the sidechain of Asp194 makes a salt link with the N-terminus at residue 16, newly formed when the A chain is cleaved in the zymogen-to-enzyme activation process. The specificity pocket is on one side of the throat of the domain 2 beta barrel, and the activation site is close next to it. | |||
The B chain consists of <scene name='Serine_Protease/Domains/1'>two domains</scene>. As is true for all of the "trypsin-like" serine proteases, each of the two thrombin domains consists mainly of a 6-stranded, antiparallel beta barrel. The specificity pocket (here filled with the Lys sidechain of the PPACK inhibitor) is in one side of the throat of the domain 2beta barrel, and the activation site is close next to it. | |||
Active site residues Ser195, Asp102, and His57 are viewed in ball and stick form.' scene='58/583418/Thombin_main_secondary/2'> | |||
==Allostery== | ==Allostery== | ||
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**[[1a0h]] - bMThr | **[[1a0h]] - bMThr | ||
}} | }} | ||
== References == | == References == | ||
<references/> | <references/> | ||
With participation by [[User:Cody Couperus]] | |||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||