1hlt
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THE STRUCTURE OF A NONADECAPEPTIDE OF THE FIFTH EGF DOMAIN OF THROMBOMODULIN COMPLEXED WITH THROMBIN
OverviewOverview
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.
DiseaseDisease
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 StructureAbout this Structure
1HLT is a Protein complex structure of sequences from Homo sapiens with CH2 as ligand. Full crystallographic information is available from OCA.
ReferenceReference
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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