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<StructureSection load='1ppb' size='350' side='right' scene='' caption='Human thrombin large (red) and small (green) subunits complex with prolinamide derivative (PDB code [[1ppb]])'>
<StructureSection load='1ppb' size='350' side='right' scene='' caption='Human thrombin large (red) and small (green) subunits complex with prolinamide derivative (PDB code [[1ppb]])'>
__TOC__
==Introduction==
==Introduction==
'''Thrombin''' (Thr) is a serine protease.  '''Prothrombin''' (PThr) is cleaved to form Thr in the coagulation cascade.  The first step of the cleavage is at residue R320 and produces '''meizothrombin''' (MThr). Thr catalyzes the conversion of fibrinogen to the insoluble fibrin.  Thr is composed of heavy chain (HC) and light chain (LC).  Prethrombin-1 lacks 155 N-terminal residues of PThr and is composed of a single polypeptide chain.  '''Prethrombin-2''' is the product of proteolysis of '''prethrombin-1''' by trypsin or by active factor X.  P-PACK Thr is a chemically modified Thr with inactivated catalytic site and active anion binding site.  [[Hirudin]] is the most potent natural inhibitor of Thr ([[Sean Swale/Human Thrombin Inhibitor]]).  For some more details see [[Serine Proteases]]. Prothrombin cleavage results in the creation of thrombin, a coagulative agent in plasma and is connected to fibrinolysis and platelet activation. During this process several peptides involved in the conversion are released into the plasma, and the remaining protein splits into two portions(http://www.uniprot.org/citations/3759958). It has been shown that prothrombin has a statistically significant connection to the occurrence of ischemic stroke with the presence of the G20210A mutation, though the cause was not isolated to prothrombin alone (http://www.uniprot.org/citations/15534175) (these links added by Connor Gramazio).  Some additional details in<br />
'''Thrombin''' (Thr) is a serine protease.  '''Prothrombin''' (PThr) is cleaved by prothrombinase at 2 cleavage sites to form the 2 chains of Thr in the coagulation cascade<ref>PMID:23809130</ref>.  The first step of the cleavage is at residue R320 and produces '''meizothrombin''' (MThr)<ref>PMID:22815477</ref>. Thr catalyzes the conversion of fibrinogen to the insoluble fibrin.  Thr is composed of heavy chain (HC) and light chain (LC).  '''Prethrombin-1''' lacks 155 N-terminal residues of PThr and is composed of a single polypeptide chain.  '''Prethrombin-2''' is the product of proteolysis of '''prethrombin-1''' by trypsin or by active factor X.  P-PACK Thr is a chemically modified Thr with inactivated catalytic site and active anion binding site.  [[Hirudin]] is the most potent natural inhibitor of Thr ([[Sean Swale/Human Thrombin Inhibitor]]).  For some more details see [[Serine Proteases]]. Prothrombin cleavage results in the creation of thrombin, a coagulative agent in plasma and is connected to fibrinolysis and platelet activation. During this process several peptides involved in the conversion are released into the plasma, and the remaining protein splits into two portions(http://www.uniprot.org/citations/3759958). It has been shown that prothrombin has a statistically significant connection to the occurrence of ischemic stroke with the presence of the G20210A mutation, though the cause was not isolated to prothrombin alone (http://www.uniprot.org/citations/15534175) (these links added by Connor Gramazio).  Some additional details in<br />
* [[Ann Taylor 115]]<br />
* [[Ann Taylor 115]]<br />
* [[Sean Swale/Human Thrombin Inhibitor]]<br />
* [[Sean Swale/Human Thrombin Inhibitor]]<br />
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[[Image:Cation pi.png|450px|center|thumb| A cation-π interaction between Trp128 and Arg 129 in alpha thrombin (PDB: 2BDY). The guanidinium carbon is 3.6 angstroms from the top edge of the Trp. It is expected that the epsilon nitrogen forms the primary cation-π interaction. The electrostatic and Van der Waals interaction energies were calculated to be -3.29 kcal/mol and -3.08 kcal/mol respectively by the CaPTURE program (http://capture.caltech.edu/result.cgi).]]
[[Image:Cation pi.png|450px|center|thumb| A cation-π interaction between Trp128 and Arg 129 in alpha thrombin (PDB: 2BDY). The guanidinium carbon is 3.6 angstroms from the top edge of the Trp. It is expected that the epsilon nitrogen forms the primary cation-π interaction. The electrostatic and Van der Waals interaction energies were calculated to be -3.29 kcal/mol and -3.08 kcal/mol respectively by the CaPTURE program (http://capture.caltech.edu/result.cgi).]]
{{Clear}}
{{Clear}}
</StructureSection>


== 3D Structures of thrombin==
== 3D Structures of thrombin==
[[Thrombin 3D Structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*'''Thrombin'''
 
**[[3pmb]] - bThr HC + LC – bovine<br />
**[[3qgn]], [[4rkj]], [[5jdu]] - hThr HC (mutant) + LC – human<br />
**[[3r3g]] - hThr HC + LC <br />
**[[2hnt]]– hThr-γ HC + LC<br />
**[[3jz1]], [[3jz2]], [[2od3]] - hThr HC + LC (mutant) <br />
**[[3gic]] - hThr HC + LC<br />
**[[3ee0]], [[2a0q]], [[1sg8]], [[1sgi]], [[1jou]] - hThr HC (mutant) + LC<br />
**[[3edx]], [[3hk3]], [[3hk6]] - mThr HC (mutant) + LC – mouse<br />
**[[2ocv]] - mThr HC + LC
 
*Thrombin complexes with small molecule
 
**[[3pma]] – bThr HC + LC residues 336-364 + sucrose octasulfate<br />
**[[1bhx]], [[1abj]], [[1ppb]] - hThr HC + LC + inhibitor<br />
**[[4rn6]] - hThr HC (mutant) + inhibitor<br />
**[[1uvs]], [[1uvt]], [[1uvu]] - bThr HC + LC + inhibitor<br />
**[[1etr]], [[1ets]], [[1ett]] – bThr-ε HC + LC + inhibitor<br />
**[[3dd2]] - hThr HC + LC + RNA<br />
**[[1hao]], [[1hap]], [[1hut]] - hThr HC + LC + DNA<br />
**[[3bf6]] - hThr HC + LC + suramin<br />
**[[1xmn]] - hThr HC + LC + heparin<br />
**[[2h9t]] - hThr HC + LC + suramin + PPACK<BR />
**[[1z8i]], [[1z8j]] - hThr HC + LC (mutant) + PPACK<BR />
**[[1sfq]], [[1shh]], [[2thf]], [[1thp]], [[1b7x]], [[4rko]] - hThr HC (mutant) + LC + PPACK<BR />
**[[1ook]] - hThr HC + LC + PPACK<BR />
**[[2hpp]], [[2hpq]] - hThr HC + LC + PThr residues 214-292 + PPACK<BR />
 
*Thrombin complexes with peptide
 
**[[1dlk]] - bThr HC + LC + peptide inhibitor<br />
**[[3hki]] - mThr HC (mutant) + LC + proteinase-activated receptor 1 peptide<br />
**[[3hkj]] - hThr HC (mutant) + LC + proteinase-activated receptor 1 peptide<br />
**[[2pux]] - mThr HC + LC + proteinase-activated receptor 3 peptide<br />
**[[2pv9]] - mThr HC (mutant) + LC + proteinase-activated receptor 4 peptide<br />
**[[1dm4]] - mThr HC (mutant) + LC + fibrinogen peptide<br />
**[[1ycp]], [[1bbr]] – bThr-ε HC + LC + fibrinogen peptide<br />
**[[1ucy]] - bThr HC + LC + fibrinogen peptide<br />
**[[1fph]] - hThr HC + LC + fibrinogen peptide<br />
**[[3bv9]] - hThr HC (mutant) + LC + peptide inhibitor<br />
**[[2a2x]], [[1eb1]], [[1h8i]], [[1h8d]], [[1dit]], [[1hbt]], [[3u8t]] - hThr HC + LC + peptide inhibitor<br />
**[[1g37]], [[1eoj]], [[1eol]], [[1nrn]], [[1nro]], [[1nrp]], [[1nrq]], [[1nrr]], [[1nrs]] - hThr HC + peptide inhibitor<br />
**[[1hlt]] - hThr HC + LC + thrombomodulin peptide<br />
**[[4ch2]], [[4ch8]] - hThr HC + LC + platelet glycoprotein IB α chain peptide <br />
**[[2ank]], [[3po1]] - hThr HC + LC + peptide + inhibitor<br />
**[[5gim]] - hPThr HC + LC + peptide<br />
 
*Thrombin complexes containing hirudin
 
**[[3c27]], [[2zc9]], [[2zda]], [[2zdv]], [[3egk]], [[2r2m]], [[2v3h]], [[2v3o]], [[2pks]], [[3eq0]], [[3dt0]], [[3dux]], [[3da9]], [[3dhk]], [[2znk]], [[2zo3]], [[3d49]], [[2zhe]], [[2zhf]], [[2zhw]], [[2zg0]], [[2zfq]], [[2zfr]], [[2zhq]], [[2zi2]], [[2ziq]], [[2zff]], [[2zfp]], [[2zgb]], [[2zgx]], [[2zf0]], [[3biu]], [[3biv]], [[2uuj]], [[2uuk]], [[2jh0]], [[2jh5]], [[2jh6]], [[2gde]], [[2bxt]], [[2bxu]], [[2bvr]], [[2bvs]], [[2bvx]], [[2bdy]], [[2feq]], [[2c8w]], [[2c8x]], [[2c8y]], [[2c8z]], [[2c90]], [[2c93]], [[2cf8]], [[2cf9]], [[2anm]], [[2w7g]], [[2fes]], [[1ype]], [[1ypg]], [[1ypj]], [[1ypk]], [[1ypl]], [[1ypm]], [[1vzq]], [[1way]], [[1wbg]], [[1riw]], [[1mu6]], [[1mu8]], [[1mue]], [[1nzq]], [[1o0d]], [[1oyt]], [[1o2g]], [[1gj4]], [[1gj5]], [[1kts]], [[1ktt]], [[1ghv]], [[1ghw]], [[1ghx]], [[1ghy]], [[1c5n]], [[1c5o]], [[1c4y]], [[1d3d]], [[1d3p]], [[1d3q]], [[1d3t]], [[1c4u]], [[1c4v]], [[1c1u]], [[1c1v]], [[1c1w]], [[1qj1]], [[1qj6]], [[1qj7]], [[1qhr]], [[1qur]], [[1d4p]], [[1ba8]], [[1bb0]], [[1ca8]], [[1awf]], [[1awh]], [[1bcu]], [[1a61]], [[1a3b]], [[1a3e]], [[1a46]], [[1a5g]], [[1b5g]], [[1tbz]], [[1a4w]], [[1ay6]], [[1ae8]], [[1afe]], [[1ad8]], [[1ai8]], [[1aix]], [[1bmm]], [[1bmn]], [[1lhc]], [[1lhd]], [[1lhe]], [[1lhf]], [[1lhg]], [[1uma]], [[1aht]], [[1fpc]], [[1w7g]], [[3ldx]], [[3p17]], [[3qto]], [[3qtv]], [[3qwc]], [[3qx5]], [[3rlw]], [[3rly]], [[3rm0]], [[3rm2]], [[3rml]], [[3rmm]], [[3rmn]], [[3rmo]], [[3t5f]], [[3sv2]], [[3si3]], [[3si4]], [[3sha]], [[3shc]], [[3u98]], [[3u9a]], [[3uwj]], [[4e7r]], [[6eo8]], [[6eo9]], [[4loy]] - hThr HC + LC + hirudin peptide + inhibitor<br />
**[[1zgi]], [[1zgv]], [[1zrb]], [[1z71]], [[1xm1]], [[1sl3]], [[1ta2]], [[1ta6]], [[1nm6]], [[1nt1]], [[1doj]], [[1d9i]], [[1d6w]], [[1qbv]], [[1tmu]], [[1dwb]], [[1dwc]], [[1dwd]], [[1dwe]], [[4baq]], [[4bao]], [[4ban]], [[4bak]], [[4bam]], [[4bah]], [[5lpd]], [[5ahg]], [[5afz]], [[5afy]], [[5af9]], [[5a2m]], [[4yes]], [[4ufg]], [[4uff]], [[4ufe]], [[4ufd]], [[4ueh]], [[4ue7]], [[4udw]], [[4ud9]] - hThr HC + hirudin peptide + inhibitor<br />
**[[1ny2]], [[8kme]], [[7kme]], [[1a2c]], [[1tom]], [[1hdt]], [[1tmt]], [[1tmb]], [[3u8o]], [[3u8r]] - hThr HC + LC + hirudin peptide + peptide inhibitor<br />
**[[3hat]] - hThr HC + LC + hirudin peptide + fibrinogen peptide<br />
**[[2uuf]], [[2pw8]], [[1no9]], [[1c5l]], [[1vr1]], [[4thn]], [[5gds]], [[1hxf]], [[1hxe]], [[1abi]], [[1hgt]], [[1ihs]], [[1iht]], [[1thr]], [[1ths]], [[2hgt]], [[3utu]], [[4ayv]], [[4ayy]], [[4az2]], [[3htc]], [[4htc]]  - hThr HC + LC + hirudin peptide<br />
**[[3vxe]], [[3vxf]] - hThr HC + LC + bivalirudin peptide<br />
**[[4mlf]] - hThr HC (mutant) + LC + hirudin peptide<br />
**[[5mm6]], [[5mls]], [[5mjt]] - hThr HC (mutant) + LC + hirudin peptide + inhibitor<br />
**[[1vit]], [[1hrt]] - bThr HC + LC + hirudin peptide<br />
 
*Thrombin complex with protein
 
**[[2a45]] - hThr HC + LC + fibrinogen α, β, γ chains<br />
**[[2a1d]], [[1nu7]] – bThr HC + LC + staphylocoagulase<br />
**[[1tb6]] - hThr HC + LC (mutant) + antithrombin<br />
**[[2b5t]] - hThr HC (mutant) + LC + antithrombin III (mutant)<br />
**[[4dt7]] - hThr HC (mutant) + LC + vitamin K-dependent protein C peptide<br />
**[[1jmo]] - hThr HC (mutant) + LC + heparin cofactor II<br />
**[[4dy7]] - hThr HC (mutant) + LC + glia-derived nexin<br />
**[[1e0f]] - hThr HC + LC + haemadin<br />
**[[4boh]] - hThr HC + LC + madanin<br />
**[[4e05]], [[4e06]] - hThr HC + LC + anophelin<br />
**[[1dx5]] - hThr HC + LC + thrombomodulin<br />
**[[3p6z]], [[3p70]] - hThr HC + LC + coagulation factor V<br />
**[[1de7]] - hThr HC + LC + factor XIII activation peptide<br />
**[[3pmh]] - hThr HC + LC + platelet glycoprotein IB α chain<br />
**[[3b23]] - hThr HC + LC + variegin<br />
**[[1avg]] - bThr HC + LC + triabin<br />
**[[1bth]] - bThr HC (mutant) + LC (mutant) + BPTI<br />
**[[1toc]] - bThr HC + LC + ornithodorin<br />
**[[1tbq]], [[1tbr]] - bThr HC + LC + rhodniin<br />
**[[5e8e]] - hThr HC + LC + antibody<br />
 
*'''Prothrombin'''
 
**[[3e6p]], [[2afq]], [[3u69]] - hPThr HC + LC<br />
**[[3s7h]], [[3s7k]]– hPThr HC + LC (mutant) <br />
**[[3bei]], [[2pgb]], [[2gp9]], [[1tq0]], [[1rd3]], [[4hzh]], [[4h6t]], [[4h6s]] - hPThr HC (mutant) + LC<br />
**[[1mh0]], [[4nzq]], [[4o03]] - hPThr HC (mutant) <br />
**[[1nl1]], [[1nl2]], [[2spt]], [[2pf1]], [[2pf2]] – bPThr residues 1-156
 
*Prothrombin complexes
 
**[[3qdz]] – hPThr HC (mutant) + LC + proteinase-activated receptor 4 peptide<br />
**[[3lu9]], [[3bef]] - hPThr HC + LC (mutant) + proteinase-activated receptor 1 peptide<br />
**[[1sr5]] - hPThr HC + LC + antithrombin III<br />
**[[3k65]] - hPThr HC residues 315-622 (mutant) + LC residues 199-314<br />
**[[3f68]] - hPThr HC residues 364-622 + LC residues 328-363 + hirudin peptide<br />
**[[1jwt]], [[3c1k]] - hPThr HC + inhibitor<br />
**[[4hfp]] - hPThr HC (mutant) + LC + inhibitor<br />
**[[2pgq]], [[1tq7]] - hPThr HC (mutant) + LC + PPACK<BR />
**[[2cn0]], [[1t4u]], [[1t4v]], [[1sb1]], [[1k21]], [[1k22]], [[1g30]], [[1g32]], [[1o5g]], [[3tu7]], [[4lxb]], [[5lce]] - hPThr HC + LC + hirudin peptide + inhibitor<br />
**[[4ax9]] - hPThr HC + LC + hirudin peptide<br />
**[[1twx]] - hPThr HC (mutant) + LC + hirudin peptide<br />
**[[2hwl]] - hPThr HC (mutant) + LC + fibrinogen γ’ peptide<br />
**[[4i7y]], [[5ew2]], [[5ew1]], [[5cmx]] - hPThr HC + LC + DNA<br />
**[[5do4]] - hPThr HC + LC + RNA<br />
 
*Prothrombin complex with protein
 
**[[1id5]] - hPThr HC + LC + ecotin<br />
**[[1p8v]] - hPThr HC + LC + platelet glycoprotein IB α chain<br />
**[[3gis]] - hPThr HC residues 364-622 (mutant) + LC residues 315-363 + thrombomodulin<br />
**[[3b9f]] - hPThr HC (mutant) + LC + protein C inhibitor<br />
**[[2ody]] - hPThr HC + LC + boophilin<br />
**[[5nhu]] - hPThr HC + LC + CE5 anticoagulant<br />
**[[5l6n]] - hPThr HC + LC + madanin<br />
 
*'''Prethrombin-1'''
 
**[[3nxp]] - hThr residues 199-622
 
*'''Prethrombin-2'''
 
**[[1nu9]] – hThr + staphylocoagulase<br />
**[[1mkw]], [[1mkx]] – hThr + bThr HC + LC<br />
**[[1hag]], [[1hah]] – hThr + hirudin peptide<br />
**[[1hai]] – hThr + inhibitor<br />
**[[3sqe]], [[3sqh]] - hThr (mutant)
 
*'''Meizothrombin'''
 
**[[1a0h]] - bMThr
}}


== References ==
== References ==

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Cody Couperus, Joel L. Sussman
Retrieved from "https://proteopedia.openfox.io/w/Thrombin"