From Proteopedia
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| - | [[Image:1zaq.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1zaq| PDB=1zaq | SCENE= }} | | {{STRUCTURE_1zaq| PDB=1zaq | SCENE= }} |
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| - | '''FOURTH EGF-LIKE DOMAIN OF THROMBOMODULIN, NMR, 12 STRUCTURES'''
| + | ===FOURTH EGF-LIKE DOMAIN OF THROMBOMODULIN, NMR, 12 STRUCTURES=== |
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| - | ==Overview==
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| - | The fourth EGF-like domain of thrombomodulin (TM4), residues E346-F389 in the TM sequence, has been synthesized. Refolding of the synthetic product under redox conditions gave a single major product. The disulfide bonding pattern of the folded, oxidized domain was (1-3, 2-4, 5-6), which is the same as that found in EGF protein. TM4 was tested for TM anticoagulant activity because deletion and substitution mutagenesis experiments have shown that the fourth EGF-like domain of TM is essential for TM cofactor activity. TM4 showed no TM-like activity in two assay systems, both for inhibition of fibrin clot formation, and for cofactor activity in thrombin activation of protein C. A preliminary structure of TM4 was determined by 2D 1H NMR from 519 NOE-derived distance constraints. Distance geometry calculations yielded a single convergent structure. The structure resembles the structure of EGF and other known EGF-like domains but has some key differences. The central two-stranded beta-sheet is conserved despite the differences in the number of amino acids in the loops. The C-terminal loop formed by the disulfide bond between C372 and C386 in TM4 is five amino acids longer than the analogous loop between C33 and C42 of EGF protein. This loop appears to have a different fold in TM4 than in EGF protein. The loop forms the two outside strands of a broken, irregular tri-stranded beta-sheet, and amino acids H384-F389 lie between the two strands forming the middle strand of the sheet. Thus, although the C-terminus of EGF protein forms one of the outside strands of a tri-stranded antiparallel sheet, the C-terminus of TM4 forms the inside strand of an irregular tri-stranded parallel-anti-parallel sheet. The residues D349, E357, and E374, which were shown to be critical for cofactor activity by alanine scanning mutagenesis, all lie in a patch near the C-terminal loop, and are solvent accessible. The other critical residues, Y358 and F376, are largely buried and appear to play essential structural rather than functional roles. | + | The line below this paragraph, {{ABSTRACT_PUBMED_8528067}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8528067 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_8528067}} |
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| | ==About this Structure== | | ==About this Structure== |
| - | 1ZAQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZAQ OCA]. | + | 1ZAQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZAQ OCA]. |
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| | ==Reference== | | ==Reference== |
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| | [[Category: Protein c]] | | [[Category: Protein c]] |
| | [[Category: Thrombin]] | | [[Category: Thrombin]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:23:49 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:11:51 2008'' |
Revision as of 10:11, 27 July 2008
Template:STRUCTURE 1zaq
FOURTH EGF-LIKE DOMAIN OF THROMBOMODULIN, NMR, 12 STRUCTURES
Template:ABSTRACT PUBMED 8528067
About this Structure
1ZAQ is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.
Reference
Synthesis, activity, and preliminary structure of the fourth EGF-like domain of thrombomodulin., Meininger DP, Hunter MJ, Komives EA, Protein Sci. 1995 Sep;4(9):1683-95. PMID:8528067
Page seeded by OCA on Sun Jul 27 13:11:51 2008
