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Hirudin

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[[Image:1hic.png|left|200px|thumb|NMR Structure of Hirudin, [[1hic]]]]
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<StructureSection load='4htc' size='350' side='right' caption='Hirudin (green) complex with glycosylated thrombin small subunit (aqua) and large subunit (magenta) (PDB entry [[4htc]])' scene='41/417483/Cv/2'>
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{{STRUCTURE_1hic| PDB=1hic | SIZE=300| SCENE=Hirudin/Cv/1 |right|CAPTION=Hirudin, [[1hic]] }}
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== Function ==
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[[Hirudin]] (Hir) is a powerful anticoagulant which is found in the leech salivary glands. It is an inhibitor of thrombin (Thr) which converts [[Fibrinogen|fibrinogen]] to [[Fibrin|fibrin]] upon blood clotting<ref>PMID:9579630</ref>. Thrombin is produced upon enzymatic cleavage of prothrombin (ProThr). '''Hirugen''' (Hirg) is a dodecapeptide of the C-terminal of Hir (sequence NDGDFEEIPEEYL). For additional details see [[Sean Swale/Human Thrombin Inhibitor]] and [[Thrombin]].
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[[Hirudin]] (Hir) is a powerful anticoagulant which is found in the leech salivary glands. It is an inhibitor of thrombin (Thr) which converts fibrinogen to fibrin upon blood clotting. Thrombin is produced upon enzymatic cleavage of prothrombin (ProThr). Hirugen (Hirg) is a dodecapeptide of the C-terminal of Hir (sequence NDGDFEEIPEEYL). The images at the left and at the right correspond to one representative Hirudin, ''i.e.'' the NMR Structure of Hirudin ([[1hic]]).
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== Relevance ==
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Hirudin is an effective local treatment in patients with mild to moderate bruises<ref>PMID:11863317</ref>. Hirudin was approved as treatment of heparin-induced thrombocytopenia and unstable angina<ref>PMID:8198374</ref>.
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== Structural highlights ==
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The <scene name='41/417483/Cv/4'>N-terminal tripeptide of hirudin (green) binds to the heavy chain of thrombin (magenta) and interacts with two of its active site residues: Ser195 and His57</scene><ref>PMID:1920434</ref>.
== 3D Structures of Hirudin ==
== 3D Structures of Hirudin ==
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[[Hirudin 3D structures]]
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</StructureSection>
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=== Hirudin ===
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== References ==
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<references/>
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[[Category:Topic Page]]
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[[1hic]], [[2hir]], [[4hir]], [[5hir]], [[6hir]] – Hir – NMR<br />
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[[2joo]] - Hir – NMR<br />
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=== Hirudin + Thrombin light and heavy chains ===
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[[1hrt]], [[3htc]], [[4htc]] - Hir +hThr L&H chains<br />
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[[3da9]] - Hir peptide+hThr L&H chains<br />
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=== Hirugen + Thrombin light and heavy chains ===
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[[2zhe]], [[2zhf]], [[2zhw]], [[2zg0]], [[2zfq]], [[2zfr]], [[1c5l]], [[1hxf]], [[1hah]], [[1hai]], [[1abi]], [[1abj]], [[1hgt]], [[2uuf]] - Hirg+ hThr L&H chains<br />
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=== Hirugen + Prothrombin ===
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[[2cn0]], [[3c1k]] – Hirg+ hProThr
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[[1t4u]], [[1t4v]], [[1o5g]], [[1g30]], [[1g32]] - Hirg+hProThr+inhibitor <br />
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=== Hirugen + Prethrombin ===
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[[1hag]] – Hirg+hPreThr<br />
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=== Hirugen + Thrombin heavy chain ===
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[[1nm6]] – Hirg+ hThr H chain<br />
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[[1nt1]] - Hirg+ hThr H chain+inhibitor<br />
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== Hirugen + Thrombin light and heavy chains+inhibitor ==
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[[1fph]] - Hirg +hThr L&H chains+polypeptide<br />
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[[1hxe]] - Hirg +hThr L&H chains+Rb<br />
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[[1ypk]], [[1riw]], [[1mu6]], [[1mu8]], [[1mue]], [[1no9]], [[1oyt]], [[1o2g]], [[1ny2]], [[1gj4]], [[1gj5]], [[1kts]], [[1ktt]], [[1ghv]], [[1ghw]], [[1ghx]], [[1ghy]], [[1h8i]], [[1h8d]], [[1c5n]], [[1c5o]], [[1c1u]], [[1c1v]], [[1c1w]], [[1qj1]], [[1qj6]], [[1qj7]], [[1qbv]], [[1bcu]], [[1a2c]], [[1a61]], [[1a46]], [[1a5g]], [[1b5g]], [[1ad8]], [[1ai8]], [[1tom]], [[1bmm]], [[1bmn]], [[1lhc]], [[1lhd]], [[1lhe]], [[1lhf]], [[1lhg]], [[1uma]], [[1aht]], [[1fpc]], [[3hat]], [[1tmu]], [[1dwb]], [[1dwc]], [[1dwd]], [[1dwe]], [[1tmb]], [[3f68]], [[3eq0]], [[3dt0]], [[3dux]], [[3dhk]], [[2znk]], [[2zo3]], [[3d49]], [[2zhq]], [[2zi2]], [[2ziq]], [[2zff]], [[2zfp]], [[2zgb]], [[2zgx]], [[2zf0]], [[2zc9]], [[2zda]], [[2zdv]], [[3egk]], [[2pw8]], [[3c27]], [[2r2m]], [[2cf8]], [[2cf9]], [[2bdy]], [[2v3h]], [[2v3o]], [[1w7g]], [[1ype]], [[1ypg]], [[1ypj]], [[3biu]], [[3biv]], [[1doj]], [[1ypl]], [[1ypm]], [[1vzq]], [[1way]], [[1wbg]], [[1k21]], [[1k22]] – Hirg+ hThr L&H chains+inhibitor<br />
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=== Hirugen+Thrombin light and heavy chains+epsilon-thrombin ===
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[[1vit]] - Hirg+hThr L&H chains+epsilon-hThr<br />
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=== Hirugen+ α-Thrombin +inhibitor ===
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[[1zrb]], [[1z71]], [[1sl3]], [[1ta2]], [[1ta6]], [[1zgi]], [[1zgv]], [[2uuk]], [[2uuj]], [[2jh0]], [[2jh5]], [[2jh6]], [[2c8w]], [[2c8x]], [[2c8y]], [[2c8z]], [[2c90]], [[2c93]] – Hirg+α-hThr+inhibitor<br />
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Current revision

Hirudin (green) complex with glycosylated thrombin small subunit (aqua) and large subunit (magenta) (PDB entry 4htc)

Drag the structure with the mouse to rotate

References

  1. ↑ Fenton JW 2nd, Ofosu FA, Brezniak DV, Hassouna HI. Thrombin and antithrombotics. Semin Thromb Hemost. 1998;24(2):87-91. PMID:9579630 doi:http://dx.doi.org/10.1055/s-2007-995828
  2. ↑ Stamenova PK, Marchetti T, Simeonov I. Efficacy and safety of topical hirudin (Hirudex): a double-blind, placebo-controlled study. Eur Rev Med Pharmacol Sci. 2001 Mar-Apr;5(2):37-42. PMID:11863317
  3. ↑ Johnson PH. Hirudin: clinical potential of a thrombin inhibitor. Annu Rev Med. 1994;45:165-77. PMID:8198374 doi:http://dx.doi.org/10.1146/annurev.med.45.1.165
  4. ↑ Rydel TJ, Tulinsky A, Bode W, Huber R. Refined structure of the hirudin-thrombin complex. J Mol Biol. 1991 Sep 20;221(2):583-601. PMID:1920434

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