ZINC-DEPENDENT DIMERS OBSERVED IN CRYSTALS OF HUMAN ENDOSTATIN

The crystal structure of human endostatin reveals a zinc-binding site. Atomic absorption spectroscopy indicates that zinc is a constituent o f both human and murine endostatin in solution. The human endostatin z inc 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 or dered around the zinc makes a dimeric contact in human endostatin crys tals. The location of the zinc site at the amino terminus, immediately adjacent to the precursor cleavage site, suggests the possibility tha t the zinc may be involved in activation of the antiangiogenic activit y following cleavage from the inactive collagen XVIII precursor or in the cleavage process itself.