Zinc-dependent dimers observed in crystals of human endostatin

Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10443-8. doi: 10.1073/pnas.95.18.10443.

Abstract

The crystal structure of human endostatin reveals a zinc-binding site. Atomic absorption spectroscopy indicates that zinc is a constituent of both human and murine endostatin in solution. The human endostatin zinc site is formed by three histidines at the N terminus, residues 1, 3, and, 11, and an aspartic acid at residue 76. The N-terminal loop ordered around the zinc makes a dimeric contact in human endostatin crystals. The location of the zinc site at the amino terminus, immediately adjacent to the precursor cleavage site, suggests the possibility that the zinc may be involved in activation of the antiangiogenic activity following cleavage from the inactive collagen XVIII precursor or in the cleavage process itself.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Collagen / chemistry*
  • Collagen / metabolism
  • Collagen Type XVIII
  • Crystallography, X-Ray
  • DNA Primers
  • Dimerization
  • Endostatins
  • Heparin / metabolism
  • Humans
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Zinc / chemistry*

Substances

  • Collagen Type XVIII
  • DNA Primers
  • Endostatins
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Heparin
  • Collagen
  • Zinc

Associated data

  • PDB/1BNL