1HLT

THE STRUCTURE OF A NONADECAPEPTIDE OF THE FIFTH EGF DOMAIN OF THROMBOMODULIN COMPLEXED WITH THROMBIN

Summary for 1HLT

• Entry DOI: 10.2210/pdb1hlt/pdb
• Related PRD ID: PRD_000020
• Descriptor: ALPHA-THROMBIN (SMALL SUBUNIT), ALPHA-THROMBIN (LARGE SUBUNIT), Thrombomodulin, ... (5 entities in total)
• Functional Keywords: serine proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 68992.96

Authors

Tulinsky, A.,Mathews, I.I. (deposition date: 1994-08-28, release date: 1994-12-20, Last modification date: 2024-11-13)

Primary citation

Mathews, I.I.,Padmanabhan, K.P.,Tulinksy, A.,Sadler, J.E.
Structure of a nonadecapeptide of the fifth EGF domain of thrombomodulin complexed with thrombin.
Biochemistry, 33:13547-13552, 1994

PubMed Abstract: 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.

PubMed: 7947765
DOI: 10.1021/bi00250a006

Experimental method

X-RAY DIFFRACTION (3 Å)