1dqb
From Proteopedia
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NMR STRUCTURE OF THROMBOMODULIN EGF(4-5)
Contents |
Overview
A glycosylated fragment of thrombomodulin containing two epidermal growth factor-like domains (TMEGF45) was analyzed by NMR. The 4th-domains structure of this two-domain fragment is similar to that of the individual domain previously determined. The 5th-domain, which has uncrossed disulfide bonds, is not as well determined in the two-domain fragment than the individual domain previously solved. The flexibility of the 5th-domain is consistent with low heteronuclear NOEs. In the individual 5th-domain, Met 388 was disordered, and key thrombin binding residues formed a hydrophobic core. By contrast, in TMEGF45, Met 388 is in the 5th-domain core, positioned by Phe 376 from the 4th-domain. As a result, key thrombin binding residues that were in the core of the individual domain are expelled. Upon thrombin binding, chemical shifts of two residues in the 4th-domain, the three interdomain linker residues, and nearly all of the 5th-domain are perturbed. Thus, TMEGF45 binds thrombin by an induced fit mechanism involving a flexible 5th-domain.
Disease
Known diseases associated with this structure: Myocardial infarction, susceptibility to OMIM:[188040], Thrombophilia due to thrombomodulin defect OMIM:[188040]
About this Structure
1DQB is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Solution structure of the smallest cofactor-active fragment of thrombomodulin., Wood MJ, Sampoli Benitez BA, Komives EA, Nat Struct Biol. 2000 Mar;7(3):200-4. PMID:10700277
Page seeded by OCA on Thu Feb 21 12:19:24 2008
