1dqb: Difference between revisions
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'''NMR STRUCTURE OF THROMBOMODULIN EGF(4-5)'''<br /> | '''NMR STRUCTURE OF THROMBOMODULIN EGF(4-5)'''<br /> | ||
==Overview== | ==Overview== | ||
A glycosylated fragment of thrombomodulin containing two epidermal growth | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1DQB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1DQB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DQB OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Komives, E | [[Category: Komives, E A.]] | ||
[[Category: Sampoli-Benitez, B | [[Category: Sampoli-Benitez, B A.]] | ||
[[Category: Wood, M | [[Category: Wood, M J.]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: anticoagulant]] | [[Category: anticoagulant]] | ||
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[[Category: thrombin]] | [[Category: thrombin]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:19:24 2008'' | ||
Revision as of 13:19, 21 February 2008
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NMR STRUCTURE OF THROMBOMODULIN EGF(4-5)
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Myocardial infarction, susceptibility to OMIM:[188040], Thrombophilia due to thrombomodulin defect OMIM:[188040]
About this StructureAbout this Structure
1DQB is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
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
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