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Literature summary for 3.4.21.5 extracted from

  • Newell-Caito, J.L.; Griffiths, A.E.; Fay, P.J.
    P3-P3' residues flanking scissile bonds in factor VIII modulate rates of substrate cleavage and procofactor activation by thrombin (2012), Biochemistry, 51, 3451-3459.
    View publication on PubMedView publication on EuropePMC

Organism

Organism UniProt Comment Textmining
Homo sapiens
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Source Tissue

Source Tissue Comment Organism Textmining
commercial preparation
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Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
factor VIII + H2O
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Homo sapiens ? proteolysis occurs at residues Arg372 and Arg740 in the facto VIII heavy chain and Arg1689 in the factor VIII light chain. The sequences at Arg740 and Arg1689 are more optimal for thrombin cleavage than at Arg372. Rates of thrombin cleavage at Arg372 are increased about 10fold and about 3fold compared with wild-type factor VIII when replaced with P3-P3' residues flanking Arg740 or Arg1689, respectively, and these values parallel increased rates of A2 subunit generation and procofactor activation. Positioning of more optimal residues flanking Arg372 abrogates the need for initial cleavage at Arg740 to facilitate this step ?
factor VIII mutant Q370E/I371P/V374F/A375S + H2O
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Homo sapiens ? mutation to P3-P3' residues flanking Arg740, 98% of the activtiy with wild-type ?
factor VIII mutant Q370S/I371P/V374F/A375Q + H2O
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Homo sapiens ? mutation to P3-P3' residues flanking Arg1689, 14% of the activtiy with wild-type ?