Enhancing factor VIII and VIIIa stability by combining mutations at the A2 domain interface and A1-C2 domain interface

Journal of Thrombosis and Haemostasis

Volumn 10, Issue 3, 2012, Pages 492-495

  Wakabayashi, H ^a   Griffiths, A E ^a   Fay, P J ^a  

^a UNIVERSITY OF ROCHESTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BLOOD CLOTTING FACTOR 8; BLOOD CLOTTING FACTOR 8A; HETERODIMER; PROTEIN VARIANT;

CONTROLLED STUDY; CRYSTAL STRUCTURE; GENE MUTATION; GENETIC VARIABILITY; HYDROPHOBICITY; LETTER; MUTANT; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN STABILITY; PROTEIN STRUCTURE; PROTEIN SUBUNIT; THERMOSTABILITY; WILD TYPE;

FACTOR VIII; POINT MUTATION; PROTEIN ENGINEERING;

EID: 84857597426     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2011.04597.x     Document Type: Letter

References (9)

1. Fay PJ. Activation of factor VIII and mechanisms of cofactor action. Blood Rev 2004; 18: 1-15.
2. Fay PJ, Haidaris PJ, Smudzin TM. Human factor VIIIa subunit structure. Reconstruction of factor VIIIa from the isolated A1/A3-C1-C2 dimer and A2 subunit. J Biol Chem 1991; 266: 8957-62.
3. Lollar P, Parker CG. pH-dependent denaturation of thrombin-activated porcine factor VIII. J Biol Chem 1990; 265: 1688-92.
4. Fay PJ, Jenkins PV. Mutating factor VIII: lessons from structure to function. Blood Rev 2005; 19: 15-27.
5. Wakabayashi H, Fay PJ. Identification of residues contributing to A2 domain-dependent structural stability in factor VIII and factor VIIIa. J Biol Chem 2008; 283: 11645-51.
6. Wakabayashi H, Varfaj F, Deangelis J, Fay PJ. Generation of enhanced stability factor VIII variants by replacement of charged residues at the A2 domain interface. Blood 2008; 112: 2761-9.
7. Wakabayashi H, Griffiths AE, Fay PJ. Combining mutations of charged residues at the A2 domain interface enhances factor VIII stability over single point mutations. J Thromb Haemost 2009; 7: 438-44.
8. Wakabayashi H, Griffiths AE, Fay PJ. Increasing hydrophobicity or disulfide bridging at the factor VIII A1 and C2 domain interface enhances procofactor stability. J Biol Chem 2011; 286: 25748-55.
9. Ngo JC, Huang M, Roth DA, Furie BC, Furie B. Crystal structure of human factor VIII: implications for the formation of the factor IXa-factor VIIIa complex. Structure 2008; 16: 597-606.