Advertisement

Molecular modeling annual

, Volume 4, Issue 8, pp 268–275 | Cite as

Molecular Models for the two Discoidin Domains of Human Blood Coagulation Factor V

  • Bruno O. Villoutreix
  • Philipp Bucher
  • Kay Hofmann
  • Stefan Baumgartner
  • Björn Dahlbäck
Full Paper

Abstract

Discoidin (DS) domains occur in a large variety of proteins. We have recently reported the D1 domain of galactose oxidase (GOase), a copper-containing enzyme whose structure has been determined at 1.7 Å resolution, as distant member of the DS domain family. The D1 domain of GOase consists of a five-stranded antiparallel β-sheet packing against a three-stranded antiparallel β-sheet. We here show that it is possible to build 3D models for DS domains using GOase as initial template and propose a 3D structure for the C1 and C2 domains of factor V (residues 1879-2037 and 2038-2196). Factors V (FV) and VIII (FVIII) are essential and homologous non-enzymatic cofactors in the coagulation cascade. They share the domain organization A1-A2-B-A3-C1 and C2 and their C domains are members of the DS family. The C1 and C2 domains of FV are rich in positively charged residues. Several clusters of amino acids, most likely involved in inter-domain interactions, protein-protein interactions and/or phospholipid binding, are identified. Our report opens new avenues to study the structure-function relationships of DS domains.

Keywords Protein modeling Blood coagulation Thrombosis FV FVIII 
Abbreviations APC activated protein C; FV factor V; FVa activated FV; FVIII factor VIII; FVIIIa activated FVIII; DS domain discoidin domain; 3D three-dimensional; GOase galactose oxidase; PT prothrombinase; PHD profile-fed neural network systems from Heidelberg 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Heidelberg 1998

Authors and Affiliations

  • Bruno O. Villoutreix
    • 1
  • Philipp Bucher
    • 2
  • Kay Hofmann
    • 2
  • Stefan Baumgartner
    • 2
  • Björn Dahlbäck
    • 1
  1. 1.Lund University, The Wallenberg Laboratory, Dept. of Clinical Chemistry, University Hospital, Malmö, S-205   02   Malmö, Sweden. Fax: +46-40 33 70 44; E-mail: bruno.villoutreix@klkemi.mas.lu.seSE
  2. 2.Swiss Institute for Experimental Cancer Research, Ch. des Boveresses 155, CH-1066 Epalinges, SwitzerlandCH

Personalised recommendations