Hirudin

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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'>
<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'>
== Function ==
== 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]].
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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]].
== Relevance ==
== Relevance ==
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== Structural highlights ==
== Structural highlights ==
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>.
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>.
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</StructureSection>
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== 3D Structures of Hirudin ==
== 3D Structures of Hirudin ==
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[[Hirudin 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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* Hirudin
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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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**[[3qto]] - Hir +hThr L&H chains + pyridine derivative
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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]], [[1aix]], [[1ay6]], [[1awf]], [[2hgt]], [[3da9]], [[3utu]] - Hirg+ hThr L&H chains<br />
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* Hirugen + prothrombin
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**[[2cn0]], [[3c1k]] – Hirg+ hProThr<br />
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**[[1t4u]], [[1t4v]], [[1o5g]], [[1g30]], [[1g32]], [[1twx]], [[3tu7]], [[4ax9]], [[1sb1]], [[5lce]], [[5jzy]], [[5jfd]] - 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]], [[7kme]], [[1d6w]] - 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]], [[1afe]], [[1ae8]] ,[[1a3b]], [[1a3e]], [[1vr1]], [[2bvr]], [[2bvs]], [[2bvx]], [[2bxt]], [[2bxu]], [[2gde]], [[2pks]], [[3ldx]], [[3p17]], [[1d9i]], [[1xm1]], [[6eo8]], [[6eo9]], [[1ba8]], [[1bb0]], [[1c4u]], [[1ca8]], [[1d3d]], [[1d3p]], [[1d3q]], [[1d3t]], [[1d4p]], [[1hdt]], [[1ihs]], [[1iht]], [[1o0d]], [[1qhr]], [[1tbz]], [[4ayv]], [[4ayy]], [[4az2]], [[3rlw]], [[3rly]], [[3rm0]], [[3rm2]], [[3rml]], [[3rmm]], [[3rmn]], [[3rmo]], [[3qtv]], [[3qwc]], [[3qx5]], [[4yes]] – Hirg+ hThr L&H chains+inhibitor<br />
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**[[2feq]], [[2fes]] – Hirg analog + hThr L&H chains+inhibitor<br />
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**[[3sha]], [[3shc]], [[3si3]], [[3si4]], [[3sv2]], [[3t5f]], [[3u98]], [[3u9a]], [[3uwj]], [[4ban]], [[4bao]], [[4e7r]], [[4loy]], [[5lpd]], [[5mjt]], [[5mls]], [[5mm6]], [[5ahg]], [[5afz]], [[5afy]], [[5af9]], [[5a2m]], [[4ufg]], [[4uff]], [[4ufe]], [[4ufd]], [[4ueh]], [[4ue7]], [[4udw]], [[4ud9]] – Hirg variant 2 + hThr L&H chains+inhibitor<br />
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**[[4bah]], [[4bak]], [[4bam]], [[4baq]], [[4lxb]], [[4mlf]] – Hirg variant 1 + hThr L&H chains+inhibitor<br />
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* Hirugen+Thrombin light and heavy chains+ protein
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**[[1vit]] - Hirg+hThr L&H chains+ε-hThr<br />
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**[[1nrs]] - Hirg+hThr L&H chains + receptor based peptide<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]], [[8kme]] – Hirg+α-hThr+inhibitor<br />
 
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}}
 
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

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

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

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