Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Energetic contributions and topographical organization of ligand-binding residues of tissue factor

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Ruf, Wolfram
  • Kelly, C. R.
  • Schullek, J. R.
  • Martin, D. M. A.
  • Polikarpov, I.
  • Boys, C. W. G.
  • Tuddenham, E. G. D.
  • Edgington, Thomas

publication date

  • May 1995

journal

  • Biochemistry  Journal

abstract

  • Tissue factor is the cellular receptor and macromolecular enzymatic cofactor for the serine protease coagulation factor VIIa. The ligand binding extracellular domain of tissue factor consists of two structural modules which fold similar to fibronectin type III modules, consistent with the classification of tissue factor as a member of the class 2 cytokine receptor family. On the basis of the three-dimensional structure, we here analyze the importance of tissue factor residues for binding of ligand by scanning alanine mutagenesis. The identified significant binding contacts account for as much as 80% of the calculated total free energy of ligand binding. Most residues with energetic contributions to ligand binding are well exposed to solvent, and the area for ligand interaction extends from the cleft formed by the two structural modules (residues Lys20, Ile22, Lys48, Asp58, Arg135, Phe140) to the convex-shaped edge of the three- and four-stranded sheets characterized by a patch of surface-exposed hydrophobic side chains in the amino-terminal module (residues Gln37, Asp44, Trp45, Phe76, Tyr78). The binding residues are dispersed over an extended surface area, indicating adaptation to the recognition of specific structural modules of the macromolecular ligand factor VIIa. This analysis provides detailed insight into the three-dimensional organization of the ligand docking structure of the initiating cofactor for the coagulation pathways.

subject areas

  • Aspartic Acid
  • Binding Sites
  • Extracellular Space
  • Factor VIIa
  • Humans
  • Ligands
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Structure-Activity Relationship
  • Thromboplastin
  • Tryptophan
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0006-2960

Digital Object Identifier (DOI)

  • 10.1021/bi00019a008

PubMed ID

  • 7756258
scroll to property group menus

Additional Document Info

start page

  • 6310

end page

  • 6315

volume

  • 34

issue

  • 19

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support