1hlt
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The crystallographic structure has been determined of a complex between a | + | The crystallographic structure has been determined of a complex between a nonadecapeptide from the fifth epidermal growth factor (EGF5) domain of human thrombomodulin and human D-PheProArg-alpha-thrombin. The peptide corresponds to amino acid residues Glu408-Glu426 of thrombomodulin and contains the third disulfide loop of EGF5 and its linker to EGF6. The structure was refined at 3.0-A resolution to an R-value of 0.146. There are two thrombin molecules in the asymmetric unit, and the structure in the crystal is a 2:1 thrombin complex. The folding of the peptide corresponds closely to the third disulfide loop of EGF2 of factor Xa (rms delta = 1.0 A). The peptide is squeezed between cofacial electropositive fibrinogen recognition exo sites of the two thrombin molecules. Since the peptide has a total of seven aspartic and glutamic acid residues, the principal binding interaction with thrombin is electrostatic. A major hydrophobic association, which is highly directional in such a pronounced electrostatic environment, involves a TyrIleLeu triplet of the peptide and Phe34, Leu65, Tyr76, and Ile82 (chymotrypsinogen numbering) of one thrombin molecule. The tyrosine of the peptide is sandwiched between the thrombin aromatic rings and is most likely the prime source of the specificity of the thrombomodulin-thrombin interaction. |
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Mathews, I | + | [[Category: Mathews, I I.]] |
[[Category: Tulinsky, A.]] | [[Category: Tulinsky, A.]] | ||
[[Category: CH2]] | [[Category: CH2]] | ||
[[Category: complex(serine proteinase/inhibitor)]] | [[Category: complex(serine proteinase/inhibitor)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:02:35 2008'' |
Revision as of 11:02, 21 February 2008
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THE STRUCTURE OF A NONADECAPEPTIDE OF THE FIFTH EGF DOMAIN OF THROMBOMODULIN COMPLEXED WITH THROMBIN
Contents |
Overview
The crystallographic structure has been determined of a complex between a nonadecapeptide from the fifth epidermal growth factor (EGF5) domain of human thrombomodulin and human D-PheProArg-alpha-thrombin. The peptide corresponds to amino acid residues Glu408-Glu426 of thrombomodulin and contains the third disulfide loop of EGF5 and its linker to EGF6. The structure was refined at 3.0-A resolution to an R-value of 0.146. There are two thrombin molecules in the asymmetric unit, and the structure in the crystal is a 2:1 thrombin complex. The folding of the peptide corresponds closely to the third disulfide loop of EGF2 of factor Xa (rms delta = 1.0 A). The peptide is squeezed between cofacial electropositive fibrinogen recognition exo sites of the two thrombin molecules. Since the peptide has a total of seven aspartic and glutamic acid residues, the principal binding interaction with thrombin is electrostatic. A major hydrophobic association, which is highly directional in such a pronounced electrostatic environment, involves a TyrIleLeu triplet of the peptide and Phe34, Leu65, Tyr76, and Ile82 (chymotrypsinogen numbering) of one thrombin molecule. The tyrosine of the peptide is sandwiched between the thrombin aromatic rings and is most likely the prime source of the specificity of the thrombomodulin-thrombin interaction.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930], Myocardial infarction, susceptibility to OMIM:[188040], Thrombophilia due to thrombomodulin defect OMIM:[188040]
About this Structure
1HLT is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Structure of a nonadecapeptide of the fifth EGF domain of thrombomodulin complexed with thrombin., Mathews II, Padmanabhan KP, Tulinksy A, Sadler JE, Biochemistry. 1994 Nov 22;33(46):13547-52. PMID:7947765
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