1dqb

NMR STRUCTURE OF THROMBOMODULIN EGF(4-5)

spinqualitylabelsall models 1dqb Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1dqb is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 12 models Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease TRBM_HUMAN Defects in THBD are the cause of thrombophilia due to thrombomodulin defect (THPH12) [MIM:614486. A hemostatic disorder characterized by a tendency to thrombosis. Defects in THBD are a cause of susceptibility to hemolytic uremic syndrome atypical type 6 (AHUS6) [MIM:612926. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype. Function TRBM_HUMAN Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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