Standard Article

Gla-Domain

Part 9. Calcium

GLA-Domains

  1. Mark A Brown,
  2. Johan Stenflo

Published Online: 15 APR 2006

DOI: 10.1002/0470028637.met049

Handbook of Metalloproteins

Handbook of Metalloproteins

How to Cite

Brown, M. A. and Stenflo, J. 2006. Gla-Domain. Handbook of Metalloproteins. 9.

Author Information

  1. Lund University, University Hospital, Malmö, Sweden

Publication History

  1. Published Online: 15 APR 2006

Abstract

The term ‘Gla-domain’ is used to describe the γ-carboxyglutamic acid (Gla)-containing region of certain vitamin K–dependent proteins such as prothrombin and factor IX. The domain comprises the first 45 or so amino acids at the N-terminus of these proteins and contains 9–13 Gla residues that can bind divalent metal cations in a cooperative manner, the most physiologically important being Ca2+. Binding of Ca2+ by the Gla residues induces a conformational transition in the domain that allows it to bind to phospholipid-containing membranes, a requisite step for the biological functioning of the proteins. Gla residues are also found in two proteins of bone and the extracellular matrix (bone Gla protein or osteocalcin, and matrix Gla protein), and in neurotoxic peptides synthesized by molluscs of the genus Conus, but these polypeptides are not considered to have a Gla-domain as such, and will not be discussed here.

3D Structure

Keywords:

  • gamma-carboxyglutamic acid;
  • blood coagulation;
  • hemostasis;
  • warfarin;
  • coumarin