2R7E

Crystal Structure Analysis of Coagulation Factor VIII

Summary for 2R7E

• Entry DOI: 10.2210/pdb2r7e/pdb
• Related: 1d7p
• Descriptor: Coagulation factor VIII, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: ceruloplasmin fold, cupper protein fold, c2 domain fold, acute phase, blood coagulation, disease mutation, glycoprotein, hemophilia, metal-binding, secreted, sulfation, blood clotting
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 176523.07

Authors

Stoddard, B.L.,Shen, B.W. (deposition date: 2007-09-07, release date: 2008-04-15, Last modification date: 2024-10-30)

Primary citation

Shen, B.W.,Spiegel, P.C.,Chang, C.H.,Huh, J.W.,Lee, J.S.,Kim, J.,Kim, Y.H.,Stoddard, B.L.
The tertiary structure and domain organization of coagulation factor VIII.
Blood, 111:1240-1247, 2008

PubMed Abstract: Factor VIII (fVIII) is a serum protein in the coagulation cascade that nucleates the assembly of a membrane-bound protease complex on the surface of activated platelets at the site of a vascular injury. Hemophilia A is caused by a variety of mutations in the factor VIII gene and typically requires replacement therapy with purified protein. We have determined the structure of a fully active, recombinant form of factor VIII (r-fVIII), which consists of a heterodimer of peptides, respectively containing the A1-A2 and A3-C1-C2 domains. The structure permits unambiguous modeling of the relative orientations of the 5 domains of r-fVIII. Comparison of the structures of fVIII, fV, and ceruloplasmin indicates that the location of bound metal ions and of glycosylation, both of which are critical for domain stabilization and association, overlap at some positions but have diverged at others.

PubMed: 17965321
DOI: 10.1182/blood-2007-08-109918

Experimental method

X-RAY DIFFRACTION (3.7 Å)