Thrombin

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 chemicaly 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 Ann Taylor 115 Sean Swale/Human Thrombin Inhibitor. Structure 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 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 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 . 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.

spinqualitylabelsall models Human thrombin large (red) and small (aqua) subunits complex with prolinamide derivative (PDB code 1ppb) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D Structures of thrombin3D Structures of thrombin

Updated on 11-December-2014

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• Thrombin
  • 3pmb - bThr HC + LC – bovine
    
  • 3qgn - hThr HC (mutant) + LC – human
    
  • 3r3g - hThr HC + LC
    
  • 2hnt– hThr-γ HC + LC
    
  • 3jz1, 3jz2, 2od3 - hThr HC + LC (mutant)
    
  • 3gic - hThr HC + LC
    
  • 3ee0, 2a0q, 1sg8, 1sgi, 1jou - hThr HC (mutant) + LC
    
  • 3edx, 3hk3, 3hk6 - mThr HC (mutant) + LC – mouse
    
  • 2ocv - mThr HC + LC
• Thrombin complexes
  • 3pma – bThr HC + LC residues 336-364 + sucrose octasulfate
    
  • 1dlk - bThr HC + LC + peptide inhibitor
    
  • 3hki - mThr HC (mutant) + LC + proteinase-activated receptor 1 peptide
    
  • 3hkj - hThr HC (mutant) + LC + proteinase-activated receptor 1 peptide
    
  • 2pux - mThr HC + LC + proteinase-activated receptor 3 peptide
    
  • 2pv9 - mThr HC (mutant) + LC + proteinase-activated receptor 4 peptide
    
  • 1dm4 - mThr HC (mutant) + LC + fibrinogen peptide
    
  • 1ycp, 1bbr – bThr-ε HC + LC + fibrinogen peptide
    
  • 1ucy - bThr HC + LC + fibrinogen peptide
    
  • 1fph - hThr HC + LC + fibrinogen peptide
    
  • 3bv9 - hThr HC (mutant) + LC + peptide inhibitor
    
  • 2a2x, 1eb1, 1h8i, 1h8d, 1dit, 1hbt, 3u8t - hThr HC + LC + peptide inhibitor
    
  • 1g37, 1eoj, 1eol, 1nrn, 1nro, 1nrp, 1nrq, 1nrr, 1nrs - hThr HC + peptide inhibitor
    
  • 1hlt - hThr HC + LC + thrombomodulin peptide
    
  • 4ch2, 4ch8 - hThr HC + LC + platelet glycoprotein IB α chain peptide
    
  • 2ank, 3po1 - hThr HC + LC + peptide + inhibitor
    
  • 1bhx, 1abj, 1ppb - hThr HC + LC + inhibitor
    
  • 1uvs, 1uvt, 1uvu - bThr HC + LC + inhibitor
    
  • 1etr, 1ets, 1ett – bThr-ε HC + LC + inhibitor
    
  • 3dd2 - hThr HC + LC + RNA
    
  • 1hao, 1hap, 1hut - hThr HC + LC + DNA
    
  • 3bf6 - hThr HC + LC + suramin
    
  • 1xmn - hThr HC + LC + heparin
    
  • 2h9t - hThr HC + LC + suramin + PPACK
    
  • 1z8i, 1z8j - hThr HC + LC (mutant) + PPACK
    
  • 1sfq, 1shh, 2thf, 1thp, 1b7x - hThr HC (mutant) + LC + PPACK
    
  • 1ook - hThr HC + LC + PPACK
    
  • 2hpp, 2hpq - hThr HC + LC + PThr residues 214-292 + PPACK
    
• 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, 4n3l, 4nze - hThr HC + LC + hirudin peptide + inhibitor
    
  • 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- hThr HC + hirudin peptide + inhibitor
    
  • 1ny2, 8kme, 7kme, 1a2c, 1tom, 1hdt, 1tmt, 1tmb, 3u8o, 3u8r - hThr HC + LC + hirudin peptide + peptide inhibitor
    
  • 3hat - hThr HC + LC + hirudin peptide + fibrinogen peptide
    
  • 2uuf, 2pw8, 1no9, 1c5l, 1vr1, 4thn, 5gds, 1hxf, 1hxe, 1abi, 1hgt, 1ihs, 1iht, 1thr, 1ths, 2hgt, 3utu, 4ayv, 4ayy, 4az2 - hThr HC + LC + hirudin peptide
    
  • 3vxe, 3vxf - hThr HC + LC + bivalirudin peptide
    
  • 4mlf - hThr HC (mutant) + LC + hirudin peptide
    
  • 1vit - bThr HC + LC + hirudin peptide
    
• Thrombin complex with protein
  • 2a45 - hThr HC + LC + fibrinogen α, β, γ chains
    
  • 2a1d, 1nu7 – bThr HC + LC + staphylocoagulase
    
  • 1tb6 - hThr HC + LC (mutant) + antithrombin
    
  • 2b5t - hThr HC (mutant) + LC + antithrombin III (mutant)
    
  • 4dt7 - hThr HC (mutant) + LC + vitamin K-dependent protein C peptide
    
  • 1jmo - hThr HC (mutant) + LC + heparin cofactor II
    
  • 4dy7 - hThr HC (mutant) + LC + glia-derived nexin
    
  • 1e0f - hThr HC + LC + haemadin
    
  • 4boh - hThr HC + LC + madanin
    
  • 4e05, 4e06 - hThr HC + LC + anophelin
    
  • 1dx5 - hThr HC + LC + thrombomodulin
    
  • 3p6z, 3p70 - hThr HC + LC + coagulation factor V
    
  • 1de7 - hThr HC + LC + factor XIII activation peptide
    
  • 3pmh - hThr HC + LC + platelet glycoprotein IB α chain
    
  • 3b23 - hThr HC + LC + variegin
    
  • 1avg - bThr HC + LC + triabin
    
  • 1bth - bThr HC (mutant) + LC (mutant) + BPTI
    
  • 1toc - bThr HC + LC + ornithodorin
    
  • 1tbq, 1tbr - bThr HC + LC + rhodniin
    
  • 1hrt - bThr HC + LC + hirudin
    
  • 3htc, 4htc - hThr HC + LC + hirudin
• Prothrombin
  • 3e6p, 2afq, 3u69 - hPThr HC + LC
    
  • 3s7h, 3s7k– hPThr HC + LC (mutant)
    
  • 3bei, 2pgb, 2gp9, 1tq0, 1rd3, 4hzh, 4h6t, 4h6s - hPThr HC (mutant) + LC
    
  • 1mh0 - hPThr HC (mutant)
    
  • 1nl1, 1nl2, 2spt, 2pf1, 2pf2 – bPThr residues 1-156
• Prothrombin complexes
  • 3qdz – hPThr HC (mutant) + LC + proteinase-activated receptor 4 peptide
    
  • 3lu9, 3bef - hPThr HC + LC (mutant) + proteinase-activated receptor 1 peptide
    
  • 1sr5 - hPThr HC + LC + antithrombin III
    
  • 3k65 - hPThr HC residues 315-622 (mutant) + LC residues 199-314
    
  • 3f68 - hPThr HC residues 364-622 + LC residues 328-363 + hirudin peptide
    
  • 1jwt, 3c1k - hPThr HC + inhibitor
    
  • 4hfy, 4hfp - hPThr HC (mutant) + LC + inhibitor
    
  • 2pgq, 1tq7 - hPThr HC (mutant) + LC + PPACK
    
  • 2cn0, 1t4u, 1t4v, 1sb1, 1k21, 1k22, 1g30, 1g32, 1o5g, 3tu7 - hPThr HC + LC + hirudin peptide + inhibitor
    
  • 4ax9 - hPThr HC + LC + hirudin peptide
    
  • 1twx - hPThr HC (mutant) + LC + hirudin peptide
    
  • 2hwl - hPThr HC (mutant) + LC + fibrinogen γ’ peptide
    
  • 4i7y - hPThr HC + LC + DNA
    
• Prothrombin complex with protein
  • 1id5 - hPThr HC + LC + ecotin
    
  • 1p8v - hPThr HC + LC + platelet glycoprotein IB α chain
    
  • 3gis - hPThr HC residues 364-622 (mutant) + LC residues 315-363 + thrombomodulin
    
  • 3b9f - hPThr HC (mutant) + LC + protein C inhibitor
    
  • 2ody - hPThr HC + LC + boophilin
• Prethrombin-1
  • 3nxp - hThr residues 199-622
• Prethrombin-2
  • 1nu9 – hThr + staphylocoagulase
    
  • 1mkw, 1mkx – hThr + bThr HC + LC
    
  • 1hag, 1hah – hThr + hirudin peptide
    
  • 1hai – hThr + inhibitor
    
  • 3sqe, 3sqh - hThr (mutant)
• Meizothrombin
  • 1a0h - bMThr