1DE7

INTERACTION OF FACTOR XIII ACTIVATION PEPTIDE WITH ALPHA-THROMBIN: CRYSTAL STRUCTURE OF THE ENZYME-SUBSTRATE COMPLEX

Summary for 1DE7

• Entry DOI: 10.2210/pdb1de7/pdb
• Descriptor: ALPHA-THROMBIN (LIGHT CHAIN), ALPHA-THROMBIN (HEAVY CHAIN), FACTOR XIII ACTIVATION PEPTIDE (28-37), ... (5 entities in total)
• Functional Keywords: enzyme-substrate complex, alpha-thrombin, factor xiii activation peptide, hydrolase/peptide, blood clotting, hydrolase-hydrolase substrate complex, hydrolase/hydrolase substrate
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space: P00734 P00734
• Total number of polymer chains: 6
• Total formula weight: 70065.01

Authors

Sadasivan, C.,Yee, V.C. (deposition date: 1999-11-13, release date: 2000-12-13, Last modification date: 2024-11-13)

Primary citation

Sadasivan, C.,Yee, V.C.
Interaction of the factor XIII activation peptide with alpha -thrombin. Crystal structure of its enzyme-substrate analog complex.
J.Biol.Chem., 275:36942-36948, 2000

PubMed Abstract: The serine protease thrombin proteolytically activates blood coagulation factor XIII by cleavage at residue Arg(37); factor XIII in turn cross-links fibrin molecules and gives mechanical stability to the blood clot. The 2.0-A resolution x-ray crystal structure of human alpha-thrombin bound to the factor XIII-(28-37) decapeptide has been determined. This structure reveals the detailed atomic level interactions between the factor XIII activation peptide and thrombin and provides the first high resolution view of this functionally important part of the factor XIII molecule. A comparison of this structure with the crystal structure of fibrinopeptide A complexed with thrombin highlights several important determinants of thrombin substrate interaction. First, the P1 and P2 residues must be compatible with the geometry and chemistry of the S1 and S2 specificity sites in thrombin. Second, a glycine in the P5 position is necessary for the conserved substrate conformation seen in both factor XIII-(28-37) and fibrinopeptide A. Finally, the hydrophobic residues, which occupy the aryl binding site of thrombin determine the substrate conformation further away from the catalytic residues. In the case of factor XIII-(28-37), the aryl binding site is shared by hydrophobic residues P4 (Val(34)) and P9 (Val(29)). A bulkier residue in either of these sites may alter the substrate peptide conformation.

PubMed: 10956659
DOI: 10.1074/jbc.M006076200

Experimental method

X-RAY DIFFRACTION (2 Å)