A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa.

A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa. Abstract Text:

H Wakabayashi,Q Zhou,F Varfaj,P J Fay,

BACKGROUND: Factor VIII (FVIII) is activated by thrombin to the labile FVIIIa, a heterotrimer of A1, A2 and A3C1C2 subunits, which serves as a cofactor for FIXa. A primary reason for the instability of FVIIIa is the tendency for the A2 subunit to dissociate from FVIIIa leading to an inactive cofactor and consequent loss of FXase activity. OBJECTIVE: Based on our finding of low-specific activity and a fast decay rate for a FVIII point mutation of Glu1829 to Ala (E1829A), we examined whether residue Glu1829 in the A3 subunit is important for A2 subunit retention. RESULTS: The rate of activity decay of E1829A was approximately fourteen fold faster than wild-type (wt) FVIIIa and this rate was reduced in the presence of added A2 subunit. Specific activity values for E1829A measured by one-stage and two-stage assays were approximately 14% and approximately 11%, respectively, compared with wt FVIII. Binding affinity for the A1 subunit to E1829A-A3C1C2 was comparable to wt A3C1C2 (K(d) = 20.1 +/- 3.4 nM for E1829A, 15.3 +/- 3.7 nM for wt), whereas A2 subunit affinity for the A1/A3C1C2 dimer forms was reduced by approximately 3.6-fold as a result of the mutation (K(d) = 526 +/- 107 nM for E1829A, 144 +/- 21 nM for wt). CONCLUSION: As modeling data suggest that Glu1829 is located at the A2-A3 domain interface these results are consistent with Glu1829 contributing to the interactions involved with A2 subunit retention in FVIIIa.

A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa. Publishing Authors By Initials

H Wakabayashi,Q Zhou,F Varfaj,PJ Fay,

For similar proteins: recombinant proteins research abstracts see: proteins: recombinant proteins research

PUBMED ID PMID:

MEDLINE DATE:

A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of thrombosis and haemostasis : JTH

VOLUME: 5

Page Numbers: 996-1001

Journal Abbreviation:

ISSN: 1538-7933

DAY: 26

MONTH: 02

YEAR: 2007

A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101170508

A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa. Keywords Mesh Terms:

KEYWORDS: Recombinant Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa. Information

Substance Name: Factor VIIIa

Registry Number: 72175-66-7

Grant and Affiliation Information for A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa.

AFFILIATION: Department of Biochemistry and Biophysics, University of Rochester School of Medicine, Rochester, NY 14642, USA.

Country: England

AGENCY: United States NHLBI

GRANT: HL76213

ACRONYM: HL

MEDLINETA: J Thromb Haemost

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa Related Publications

• A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa.
• Application of multiresolution spatial filters to long-axis tracking.
• Are binaural cues available for sound source localization in teleost fishs?
• C-reactive protein enhances tissue factor expression by vascular smooth muscle cells: mechanisms and in vivo significance.
• Coordinated regulation of intestinal functions in C. elegans by LIN-35/Rb and SLR-2.
• Elimination and exchange of trifluoroacetate counter-ion from cationic peptides: a critical evaluation of different approaches.
• Factor VIII A1 domain residues 97-105 represent a light chain-interactive site.
• Genetic mapping and manipulation: Chapter 1-Introduction and basics.
• Genetic mapping and manipulation: Chapter 2-Two-point mapping with genetic markers.
• Genetic mapping and manipulation: Chapter 3-Three-point mapping with genetic markers.
• Genetic mapping and manipulation: Chapter 5-SNPs: Three-point mapping.
• Genetic mapping and manipulation: Chapter 6-Mapping with deficiencies and duplications.
• Genetic mapping and manipulation: Chapter 7-Making compound mutants.
• Genetic mapping and manipulation: Chapter 9-Synthetic and enhancer mutations.
• Genetic variation in the cysteine biosynthesis pathway causes sensitivity to pharmacological compounds.
• Identification of Residues Contributing to A2 Domain-dependent Structural Stability in Factor VIII and Factor VIIIa.
• Mass spectrometry in nutrition: understanding dietary health effects at the molecular level.
• ORAL HEALTH CONDITIONS AMONG PERSONNEL OF THE CHINESE ARMY.
• Plant genome horizons: Michael Bennett's contribution to genome research.
• Plasminogen activator inhibitor-1 and restenosis.
• Punctuated genome size evolution in Liliaceae.
• Putting the public back into public health: one city's experience.
• Residues surrounding Arg336 and Arg562 contribute to the disparate rates of proteolysis of factor VIIIa catalyzed by activated protein C.
• Shoulder kinematics and kinetics during two speeds of wheelchair propulsion.
• Spectral contrasts underlying auditory stream segregation in goldfish (Carassius auratus).
• Synthetic medium for susceptibility testing.
• THE QUEQUECHAN RIVER IMPROVEMENT, FALL RIVER: A MILLION DOLLAR PROJECT IN MUNICIPAL HOUSEKEEPING.
• The C. elegans glycopeptide hormone receptor ortholog, FSHR-1, regulates germline differentiation and survival.
• Towards a Phylogeny for Coffea (Rubiaceae): Identifying Well-supported Lineages Based on Nuclear and Plastid DNA Sequences.
• Transcriptome profiling of the C. elegans Rb ortholog reveals diverse developmental roles.