3hat
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 3hat |SIZE=350|CAPTION= <scene name='initialview01'>3hat</scene>, resolution 2.5Å | |PDB= 3hat |SIZE=350|CAPTION= <scene name='initialview01'>3hat</scene>, resolution 2.5Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=SO3:SULFITE ION'>SO3</scene> | + | |LIGAND= <scene name='pdbligand=ABN:BENZYLAMINE'>ABN</scene>, <scene name='pdbligand=MBN:TOLUENE'>MBN</scene>, <scene name='pdbligand=RNG:(6,10-DIOXO-OCTAHYDRO-PYRIDAZINO[1,2-A][1,2]DIAZEPIN-1-YL)-ACETALDEHYDE+FRAGMENT'>RNG</scene>, <scene name='pdbligand=SO3:SULFITE+ION'>SO3</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3hat FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hat OCA], [http://www.ebi.ac.uk/pdbsum/3hat PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3hat RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
The structures of two mimetic inhibitor complexes of human alpha-thrombin have been determined by X-ray crystallography. One mimics a beta-turn with a bicyclic ring system; the other mimics two different active-site binding modes. The beta-turn mimetic is used to approximate a turn found in the conformation of fibrinopeptide A, which is catalytically released by thrombin in the activation of fibrinogen to fibrin. The binding of the second mimetic is a hybrid between normal substrate and the abnormal binding of the potent natural leech inhibitor hirudin. The binding of the beta-turn mimetic is tenuous, because it is like a substrate, while that of the substrate-hirudin hybrid is that of a tenacious inhibitor (which it is). Structurally retrospect modifications for rational design and improvement of both mimetic inhibitors are proposed. | The structures of two mimetic inhibitor complexes of human alpha-thrombin have been determined by X-ray crystallography. One mimics a beta-turn with a bicyclic ring system; the other mimics two different active-site binding modes. The beta-turn mimetic is used to approximate a turn found in the conformation of fibrinopeptide A, which is catalytically released by thrombin in the activation of fibrinogen to fibrin. The binding of the second mimetic is a hybrid between normal substrate and the abnormal binding of the potent natural leech inhibitor hirudin. The binding of the beta-turn mimetic is tenuous, because it is like a substrate, while that of the substrate-hirudin hybrid is that of a tenacious inhibitor (which it is). Structurally retrospect modifications for rational design and improvement of both mimetic inhibitors are proposed. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Dysprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hyperprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hypoprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 28: | Line 28: | ||
[[Category: Mathews, I I.]] | [[Category: Mathews, I I.]] | ||
[[Category: Tulinsky, A.]] | [[Category: Tulinsky, A.]] | ||
| - | [[Category: SO3]] | ||
[[Category: complex (serine protease/inhibitor)]] | [[Category: complex (serine protease/inhibitor)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:33:47 2008'' |
Revision as of 02:33, 31 March 2008
| |||||||
| , resolution 2.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ACTIVE SITE MIMETIC INHIBITION OF THROMBIN
Overview
The structures of two mimetic inhibitor complexes of human alpha-thrombin have been determined by X-ray crystallography. One mimics a beta-turn with a bicyclic ring system; the other mimics two different active-site binding modes. The beta-turn mimetic is used to approximate a turn found in the conformation of fibrinopeptide A, which is catalytically released by thrombin in the activation of fibrinogen to fibrin. The binding of the second mimetic is a hybrid between normal substrate and the abnormal binding of the potent natural leech inhibitor hirudin. The binding of the beta-turn mimetic is tenuous, because it is like a substrate, while that of the substrate-hirudin hybrid is that of a tenacious inhibitor (which it is). Structurally retrospect modifications for rational design and improvement of both mimetic inhibitors are proposed.
About this Structure
3HAT is a Single protein structure of sequence from Homo sapiens. This structure supersedes the now removed PDB entry 2HAT. Full crystallographic information is available from OCA.
Reference
Active-site mimetic inhibition of thrombin., Mathews II, Tulinsky A, Acta Crystallogr D Biol Crystallogr. 1995 Jul 1;51(Pt 4):550-9. PMID:15299843
Page seeded by OCA on Mon Mar 31 05:33:47 2008
