Proteopedia - User contributions [en]

Sandbox Reserved 348

2011-04-04T08:40:01Z

Douglas Streifel: Added images.

{{Template:Sandbox_Reserved_BCMB307}}


{{ STRUCTURE_1ppb | PDB=1ppb | SCENE=Sandbox_Reserved_348/Ligand/4 }}
[[Image:Thrombin_in_Coagulation.png|thumb|left|300px|The role of thrombin and prothrombin in [http://en.wikipedia.org/wiki/Coagulation coagulation].]]

Thrombin is a [[trypsin]]-like [[serine protease]] which is best known for its role in blood clotting. In humans, the F2 gene codes for prothrombin, which is also known as Coagulation Factor II.<ref name="Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively.">PMID:3474786</ref><ref name="Nucleotide sequence of the gene for human prothrombin.">PMID:2825773</ref> Clevage of prothrombin to form activated α-thrombin is a key step in the final common pathway of blood clotting, because clevage by thrombin activates several factors in blood clotting, especially [[fibrin]], [[factor XIII]], and [[protein C]].<ref name="Thrombin interactions.">PMID:12970119</ref>

__TOC__

==Structure==
Thrombin is comprised of two chains, often referred to as the <scene name='Sandbox_Reserved_348/Small_subunit/3'>short chain</scene> and the <scene name='Sandbox_Reserved_348/Large_subunit/3'>long chain</scene>. All known functional epitopes are found on the long chain. There is one active site, which in the case of [[1ppb]] is occupied with <scene name='Sandbox_Reserved_348/Ligand/4'>D-Phe-Pro-Arg chloromethylketone</scene>.<ref name="The refined 1.9A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment.">PMID:2583108</ref> Additionally, there are three structural disulfide bonds.
{|
|While thrombin is described as a [[trypsin]]-like [[serine protease]], it is more specific than trypsin due to two exosites which bind the substrate at a point separate from the active site. These exosites also allow for more specific inhibition, since [[protein C]] and [[factor Xa]] have similar active sites but play very different roles in the clotting process.<ref name="Thrombin interactions."/>
|[[Image:Thrombin_catalytic_triad.png|thumb|left|150px|The [[serine protease]] catalytic triad in the active site of α-thrombin, bound to D-Phe-Pro-Arg chloromethylketone ligand.]]
|}

==Regulation==
{|
|[[Image:Thrombin-Hirudin_Complex.png|thumb|left|200px|<scene name='Sandbox_Reserved_348/Hirudin/2'>α-Thrombin - Hirudin Complex</scene>]]
|Prothrombin is proteolytically activated to α-thrombin by [[factor Xa]]. α-Thrombin is permanently inactivated by the [[Serine Protease Inhibitor]] [[antithrombin]], with [[heparin]] as a cofactor, and allosterically regulated by sodium ion concentration. [[Thrombomodulin]] inhibits clevage of fibrinogen to fibrin, but also enhances α-thrombin activity with respect to [[protein C]]. Since activated protein C proteolytically inactivates earlier steps in the chain, this effectively reverses the role of thrombin from coagulant to anticoagulant.<ref name="Thrombin interactions."/>

[[Hirudin]] is a potent natural inhibitor of thrombin, produced by [http://en.wikipedia.org/wiki/Leeches leeches] such as <I>[http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis]</I>.
|}
==3D Structures==
===α-Thrombin===
*[[1ppb]]
*[[1uma]]
*[[1de7]]

===Prothrombin===
*[[2afq]]

==See Also==
*[[Fibrin]]
*[[Trypsin]]
*[[Serine Protease]]
*[[Factor Xa]]
*[[Hirudin]]

==External Resources==
*[http://en.wikipedia.org/wiki/Thrombin Thrombin] at Wikipedia
*[http://en.wikipedia.org/wiki/Serine_protease Serine protease] at Wikipedia
*[http://en.wikipedia.org/wiki/Fibrin_glue Fibrin Glue] at Wikipedia
*[http://en.wikipedia.org/wiki/Coagulation Coagulation] (blood clotting) at Wikipedia
*[http://en.wikipedia.org/wiki/Hemophilia Hemophilia] at Wikipedia

=References=
<references/>

File:Thrombin-Hirudin Complex.png

2011-04-04T08:11:53Z

Douglas Streifel: Image of the Thrombin-Hirudin complex from 4htc. Generated by me using DeepView.

== Summary ==
Image of the Thrombin-Hirudin complex from [[4htc]]. Generated by me using DeepView.
== Licensing ==
{{self|cc-by-sa-3.0}}

File:Thrombin catalytic triad.png

2011-04-04T08:05:24Z

Douglas Streifel: Image showing the serine protease catalytic triad of thrombin (HIS57, ASP102, SER195). Generated by me using DeepView.

== Summary ==
Image showing the serine protease catalytic triad of thrombin (HIS57, ASP102, SER195). Generated by me using DeepView.
== Licensing ==
{{self|cc-by-sa-3.0}}

Sandbox Reserved 345

2011-04-04T07:40:34Z

Douglas Streifel: Fixed jmol applet template call

{{Template:Sandbox_Reserved_BCMB307}}

=S-Adenosylmethionine decarboxylase=
{{STRUCTURE_3cs9|PDB=3cs9|SCENE=}}
S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the polyamine biosynthetic pathway, forming the amine decarboxylated S-adenosylmethionine <ref name="primary">PMID: 11583147</ref><ref name="two">PMID: 9353291</ref> It also aids in the synthesis of spermine and spermidine <ref name="primary"/><ref name="three">PMID: 11583148</ref><ref name="four">PMID: 12600205</ref>. Spermine and spermidine are polyamines that are essential growth factors and critical in cell differentiation <ref name="four"/><ref name="five">PMID: 19527050</ref>. Their levels within cells are regulated by the amount of AdoMetDC available <ref name="four"/>. Thus, AdoMetDC is tightly regulated in mammalian cells <ref name="primary"/>.

==Structure and Function==
S-Adenosylmethionine decarboxylase is a (αβ)2 <scene name='Sandbox_Reserved_345/proteins_subunits'>dimer</scene>, forming a four-layer αββα sandwich <ref name="primary"/>. The αβ monomers both have the same structure <ref name="primary"/>. The β chain consists of the residues 1-67 while the α chain contains the residues 68-329 <ref name="four"/>. Each β sheet contains eight anti-parallel β strands <ref name="primary"/>. AdoMetDC has a very unique fold compared to other large β-sandwich structures as well as other pyruvoyl-dependent amino acid decarboxylases <ref name="primary"/>. The two β sheets are connected by only one covalent bond which allows them a large amount of flexibility to behave as independently folded domains that move with respect to each other <ref name="primary"/>. The α and β subunits are formed by an internal cleavage reaction <ref name="primary"/>.

AdoMetDC belongs to a small class of decarboxylating enzymes that use as a prosthetic group a covalently bound pyruvate <ref name="primary"/><ref name="two"/>. The same cleavage reaction that forms the α and β subunits also converts a serine (Ser68) residue into the pyruvate <ref name="two"/><ref name="three"/><ref name="six">PMID: 10029540</ref>. This self processing reaction occurs via a N to O acyl rearrangement <ref name="three"/><ref name="four"/>. The pyruvoyl group is bound to the N-terminal of an α subunit <ref name="four"/><ref name="five"/>.
Decarboxylation of S-adenosylmethionine (AdoMet) to S-adenosyl-5’-(3-methylthiopropylamine) (dcAdoMet) is catalyzed using AdoMetDC <ref name="two"/>. Spermidine is the receptor of the aminopropyl group from dcAdoMet forming spermine or spermidine <ref name="five"/>. This is an early step in the pathway of polyamine biosynthesis of dcAdoMet, which commits it completely to this fate <ref name="five"/>.

==Mechanism:==
Binding of AdoMet to its enzyme AdoMetDC is the first step and binding occurs through the pyruvate prosthetic group, reacting to give a Schiff base <ref name="six"/>. The pyruvate then acts as an election sink, helping to break the carbon to carboxylic acid bond (C-COO-) resulting in a carbon dioxide (CO2) being eliminated <ref name="six"/>. Protonation occurs at the R carbon of the product resulting in the release of dcAdoMet <ref name="six"/>. This protonation also regenerates the pyruvate cofactor so that it is available and ready for another reaction <ref name="six"/>.
==References==
<references/>

Sandbox Reserved 348

2011-04-04T06:39:50Z

Douglas Streifel: Scene edits, added regulation section.

{{Template:Sandbox_Reserved_BCMB307}}


{{ STRUCTURE_1ppb | PDB=1ppb | SCENE=Sandbox_Reserved_348/Ligand/4 }}
[[Image:Thrombin_in_Coagulation.png|thumb|left|300px|The role of thrombin and prothrombin in [http://en.wikipedia.org/wiki/Coagulation coagulation].]]

Thrombin is a [[trypsin]]-like [[serine protease]] which is best known for its role in blood clotting. In humans, the F2 gene codes for prothrombin, which is also known as Coagulation Factor II.<ref name="Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively.">PMID:3474786</ref><ref name="Nucleotide sequence of the gene for human prothrombin.">PMID:2825773</ref> Clevage of prothrombin to form activated α-thrombin is a key step in the final common pathway of blood clotting, because clevage by thrombin activates several factors in blood clotting, especially [[fibrin]], [[factor XIII]], and [[protein C]].<ref name="Thrombin interactions.">PMID:12970119</ref>

__TOC__

==Structure==
Thrombin is comprised of two chains, often referred to as the <scene name='Sandbox_Reserved_348/Small_subunit/3'>short chain</scene> and the <scene name='Sandbox_Reserved_348/Large_subunit/3'>long chain</scene>. All known functional epitopes are found on the long chain. There is one active site, which in the case of [[1ppb]] is occupied with <scene name='Sandbox_Reserved_348/Ligand/4'>D-Phe-Pro-Arg chloromethylketone</scene>.<ref name="The refined 1.9A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment.">PMID:2583108</ref> Additionally, there are three structural disulfide bonds.

While thrombin is described as a [[trypsin]]-like [[serine protease]], it is more specific than trypsin due to two exosites which bind the substrate at a point separate from the active site. These exosites also allow for more specific inhibition, since [[protein C]] and [[factor Xa]] have similar active sites but play very different roles in the clotting process.<ref name="Thrombin interactions."/>

==Regulation==

Prothrombin is proteolytically activated to α-thrombin by [[factor Xa]]. α-Thrombin is permanently inactivated by [[antithrombin]], with [[heparin]] as a cofactor, and allosterically regulated by sodium ion concentration. [[Thrombomodulin]] inhibits clevage of fibrinogen to fibrin, but also enhances α-thrombin activity with respect to [[protein C]]. Since activated protein C proteolytically inactivates earlier steps in the chain, this effectively reverses the role of thrombin from coagulant to anticoagulant.<ref name="Thrombin interactions."/>

==3D Structures==
===α-Thrombin===
*[[1ppb]]
*[[1uma]]
*[[1de7]]

===Prothrombin===
*[[2afq]]

==See Also==
*[[Fibrin]]
*[[Trypsin]]
*[[Serine Protease]]
*[[Factor Xa]]

==External Resources==
*[http://en.wikipedia.org/wiki/Thrombin Thrombin] at Wikipedia
*[http://en.wikipedia.org/wiki/Serine_protease Serine protease] at Wikipedia
*[http://en.wikipedia.org/wiki/Fibrin_glue Fibrin Glue] at Wikipedia
*[http://en.wikipedia.org/wiki/Coagulation Coagulation] (blood clotting) at Wikipedia
*[http://en.wikipedia.org/wiki/Hemophilia Hemophilia] at Wikipedia

=References=
<references/>

Sandbox Reserved 348

2011-03-27T05:00:50Z

Douglas Streifel: Tweak 3D structures section

Sandbox Reserved 348

2011-03-27T04:51:55Z

Douglas Streifel: Added a real image, scene tweaks

File:Thrombin in Coagulation.png

2011-03-27T04:38:06Z

Douglas Streifel: This is an image summarizing the role of various factors in coagulation. It was sourced from Wikipedia at [http://en.wikipedia.org/wiki/File:Coagulation_full.svg]. I added highlighting of thrombin and prothrombin.

== Summary ==
This is an image summarizing the role of various factors in coagulation. It was sourced from Wikipedia at [http://en.wikipedia.org/wiki/File:Coagulation_full.svg]. I added highlighting of thrombin and prothrombin.
== Licensing ==
{{cc-by-sa-3.0}}

Sandbox Reserved 348

2011-03-27T04:00:30Z

Douglas Streifel: Added scenes

{{Template:Sandbox_Reserved_BCMB307}}


{{ STRUCTURE_1ppb | PDB=1ppb | SCENE=Sandbox_Reserved_348/Ligand/1 }}
[[Image:1ppb.png|thumb|left|300px|This are a caption.<ref name="Placeholder">PMID:2583108</ref>]]

Thrombin is a [[trypsin]]-like [[Serine Protease|serine protease]] which is best known for its role in blood clotting. In humans, the F2 gene codes for prothrombin, which is also known as Coagulation Factor II.<ref name="Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively.">PMID:3474786</ref><ref name="Nucleotide sequence of the gene for human prothrombin.">PMID:2825773</ref> Clevage of prothrombin to form activated α-thrombin is a key step in the final common pathway of blood clotting, because thrombin activates fibrin, which creates cross-linked fibrin clots.<ref name="Thrombin interactions.">PMID:12970119</ref>

__TOC__

==Scenes==
*<scene name='Sandbox_Reserved_348/Ligand/1'>Ligand</scene>
*<scene name='Sandbox_Reserved_348/Small_subunit/1'>Small Subunit</scene>
*<scene name='Sandbox_Reserved_348/Large_subunit/1'>Large Subunit</scene>

==3D Structures of α-Thrombin==
*[[1ppb]]
*[[1uma]]
*[[1de7]]

==3D Structures of Prothrombin==
*[[2afq]]

==See Also==
*[[Fibrin]]
*[[Trypsin]]
*[[Serine Protease]]

==External Resources==
*[http://en.wikipedia.org/wiki/Thrombin Thrombin] at Wikipedia
*[http://en.wikipedia.org/wiki/Serine_protease Serine protease] at Wikipedia
*[http://en.wikipedia.org/wiki/Fibrin_glue Fibrin Glue] at Wikipedia
*[http://en.wikipedia.org/wiki/Coagulation Coagulation] (blood clotting) at Wikipedia
*[http://en.wikipedia.org/wiki/Hemophilia Hemophilia] at Wikipedia

=References=
<references/>

Sandbox Reserved 348

2011-03-26T22:35:12Z

Douglas Streifel: Fix reference

{{Template:Sandbox_Reserved_BCMB307}}


{{ STRUCTURE_1ppb | PDB=1ppb | SCENE=Sandbox_Reserved_348/Cpk/1 }}
[[Image:1ppb.png|thumb|left|300px|This are a caption.<ref name="Placeholder">PMID:2583108</ref>]]

Thrombin is a [[trypsin]]-like [[Serine Protease|serine protease]] which is best known for its role in blood clotting. In humans, the F2 gene codes for prothrombin, which is also known as Coagulation Factor II.<ref name="Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively.">PMID:3474786</ref><ref name="Nucleotide sequence of the gene for human prothrombin.">PMID:2825773</ref> Clevage of prothrombin to form activated α-thrombin is a key step in the final common pathway of blood clotting, because thrombin activates fibrin, which creates cross-linked fibrin clots.<ref name="Thrombin interactions.">PMID:12970119</ref>

__TOC__

=3D Structures of α-Thrombin=
*[[1ppb]]
*[[1uma]]
*[[1de7]]

=3D Structures of Prothrombin=
*[[2afq]]

=See Also=
*[[Fibrin]]
*[[Trypsin]]
*[[Serine Protease]]

=External Resources=
*[http://en.wikipedia.org/wiki/Thrombin Thrombin] at Wikipedia
*[http://en.wikipedia.org/wiki/Serine_protease Serine protease] at Wikipedia
*[http://en.wikipedia.org/wiki/Fibrin_glue Fibrin Glue] at Wikipedia
*[http://en.wikipedia.org/wiki/Coagulation Coagulation] (blood clotting) at Wikipedia
*[http://en.wikipedia.org/wiki/Hemophilia Hemophilia] at Wikipedia

=References=
<references/>

Sandbox Reserved 348

2011-03-26T22:33:06Z

Douglas Streifel: Added some text

{{Template:Sandbox_Reserved_BCMB307}}


{{ STRUCTURE_1ppb | PDB=1ppb | SCENE=Sandbox_Reserved_348/Cpk/1 }}
[[Image:1ppb.png|thumb|left|300px|This are a caption.<ref name="Placeholder">PMID:2583108</ref>]]

Thrombin is a [[trypsin]]-like [[Serine Protease|serine protease]] which is best known for its role in blood clotting. In humans, the F2 gene codes for prothrombin, which is also known as Coagulation Factor II.<ref name="Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively.">PMID:3474786</ref><ref name="Nucleotide sequence of the gene for human prothrombin.">PMID:2825773</ref> Clevage of prothrombin to form activated α-thrombin is a key step in the final common pathway of blood clotting, because thrombin activates fibrin, which creates cross-linked fibrin clots.<ref name="Thrombin interactions.">12970119</ref>

__TOC__

=3D Structures of α-Thrombin=
*[[1ppb]]
*[[1uma]]
*[[1de7]]

=3D Structures of Prothrombin=
*[[2afq]]

=See Also=
*[[Fibrin]]
*[[Trypsin]]
*[[Serine Protease]]

=External Resources=
*[http://en.wikipedia.org/wiki/Thrombin Thrombin] at Wikipedia
*[http://en.wikipedia.org/wiki/Serine_protease Serine protease] at Wikipedia
*[http://en.wikipedia.org/wiki/Fibrin_glue Fibrin Glue] at Wikipedia
*[http://en.wikipedia.org/wiki/Coagulation Coagulation] (blood clotting) at Wikipedia
*[http://en.wikipedia.org/wiki/Hemophilia Hemophilia] at Wikipedia

=References=
<references/>

Sandbox Reserved 348

2011-03-26T21:46:54Z

Douglas Streifel: Added a bunch of links.

{{Template:Sandbox_Reserved_BCMB307}}


{{ STRUCTURE_1ppb | PDB=1ppb | SCENE=Sandbox_Reserved_348/Cpk/1 }}
__TOC__

=Section 1=
<scene name='Sandbox_Reserved_348/Raw/1'>Raw Scene</scene>
=Section 2=
<scene name='Sandbox_Reserved_348/Cpk/1'>CPK</scene>
=Section 3=
[[Image:1ppb.png|300px|This are a caption.]]

<ref name="Placeholder">PMID:2583108</ref>

=3D Structures of α-Thrombin=
*[[1ppb]]
*[[1uma]]
*[[1de7]]

=See Also=
*[[Fibrin]]
*[[Trypsin]]

=External Resources=
*[http://en.wikipedia.org/wiki/Thrombin Thrombin] at Wikipedia
*[http://en.wikipedia.org/wiki/Serine_protease Serine protease] at Wikipedia
*[http://en.wikipedia.org/wiki/Fibrin_glue Fibrin Glue] at Wikipedia
*[http://en.wikipedia.org/wiki/Coagulation Coagulation] (blood clotting) at Wikipedia
*[http://en.wikipedia.org/wiki/Hemophilia Hemophilia] at Wikipedia

=References=
<references/>