+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

A novel type I factor X variant due to loss of a disulfide bond in the catalytic domain



A novel type I factor X variant due to loss of a disulfide bond in the catalytic domain



Blood Coagulation & Fibrinolysis 14(4): 401-405



We report a novel mutation within the coagulation factor X (FX) that we have designated FX Padua 4. The phenotype and genotype of the proband and family members were studied. The proband was a child affected by a complex neurological syndrome who, after birth, experienced severe bleeding. The proband showed a laboratory pattern characterized by a severe reduction of FX activity and FX antigen, suggesting a true deficiency. Molecular analysis disclosed a new FX mutation localized in the catalytic domain responsible for a Cys350Phe substitution. The proband was homozygous for this mutation. The proband's mother and father showed a heterozygous pattern and had approximately one-half the normal FX activity and FX antigen. Residual purified FX Cys350Phe had an identical behavior to normal FX as showed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Molecular modeling confirms that the mutation leads to the disruption of a disulfide bridge in the catalytic region of FX. Comparison with other topologically equivalent mutations in other vitamin K-dependent proteins suggests that this disruption could adversely affect protein folding/stability, accounting for the cross-reactive material negative phenotype.

(PDF emailed within 1 workday: $29.90)

Accession: 034312644

Download citation: RISBibTeXText


Related references

A novel type I factor X variant (factor X Cys350Phe) due to loss of a disulfide bond in the catalytic domain. Blood Coagulation and Fibrinolysis 14(4): 401-405, 2003

Factor VII C329R: a variant with a disrupted disulfide bond in the catalytic domain. Blood Coagulation & Fibrinolysis 8(5): 308-310, 1997

A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity. Journal of Molecular Biology 365(5): 1460-1468, 2006

Activating mutations in the extracellular domain of the fibroblast growth factor receptor 2 function by disruption of the disulfide bond in the third immunoglobulin domain. Proceedings of the National Academy of Sciences of the United States of America 95(8): 4567-4572, April 14, 1998

Activating mutations in the extracellular domain of the fibroblast growth factor receptor 2 function by disruption of the disulfide bond in the third immunoglobulin-like domain. Proceedings of the National Academy of Sciences of the United States of America 95(8): 67-72, 1998

Conformation of factor VIIa stabilized by a labile disulfide bond (Cys-310-Cys-329) in the protease domain is essential for interaction with tissue factor. Journal of Biological Chemistry 272(41): 25724-25730, 1997

Structural and catalytic characterization of a thermally stable and acid-stable variant of human carbonic anhydrase II containing an engineered disulfide bond. Acta Crystallographica. Section D, Biological Crystallography 69(Pt 8): 1414-1422, 2013

The disulfide bond arrangement in the extracellular domain of the activin type II receptor. Journal of Protein Chemistry 18(4): 437-446, 1999

Evolution of an interloop disulfide bond in high-affinity antibody mimics based on fibronectin type III domain and selected by yeast surface display: molecular convergence with single-domain camelid and shark antibodies. Journal of Molecular Biology 368(4): 1024-1041, 2007

Disulfide bond requirements for assembly of the platelet glycoprotein Ib-binding domain of von Willebrand factor. Journal of Biological Chemistry 268(4): 2821-2827, 1993

Synergism between tissue-type plasminogen activator and a genetically engineered variant lacking the finger domain, the growth factor domain and the first kringle domain. Thrombosis and Haemostasis 65(3): 286-290, 1991

The Disulfide Bond between Cys22 and Cys27 in the Protease Domain Modulate Clotting Activity of Coagulation Factor X. Thrombosis and Haemostasis 2019, 2019

Identification of the ubiquinone-binding domain in the disulfide catalyst disulfide bond protein B. Journal of Biological Chemistry 277(3): 1649-1652, 2001

Bacitracin inhibits the reductive activity of protein disulfide isomerase by disulfide bond formation with free cysteines in the substrate-binding domain. Febs Journal 278(12): 2034-2043, 2012

Structural study of a mutant type I collagen from a patient with lethal osteogenesis imperfecta containing an intramolecular disulfide bond in the triple-helical domain. Febs Letters 198(2): 213-216, 1986