3hat
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ACTIVE SITE MIMETIC INHIBITION OF THROMBIN
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
3HAT is a Single protein structure of sequence from Homo sapiens with SO3 as ligand. This structure superseeds the now removed PDB entry 2HAT. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
ReferenceReference
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
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