Structural highlights
FunctionCOIA1_MOUSE Endostatin potently inhibits endothelial cell proliferation and angiogenesis. May inhibit angiogenesis by binding to the heparan sulfate proteoglycans involved in growth factor signaling. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedEndostatin is a proteolytic fragment of collagen XVIII that potently inhibits angiogenesis and tumour growth. Human endostatin contains a zinc ion, bound near the N terminus, which was not observed in the original structure of mouse endostatin at pH 5. Controversial data exist on the role of this zinc ion in the anti-tumour activity. We report two new crystal structures of mouse endostatin at pH 8.5 with bound zinc. One crystal form shows a metal ion coordination similar to that in human endostatin (His132, His134, His142, Asp207), but the conformation of the N-terminal segment is different. In the other crystal form, Asp136 replaces His132 as a zinc ligand. Site-directed mutagenesis of zinc-binding residues demonstrates that both coordination geometries occur in solution. The large degree of structural heterogeneity of the zinc-binding site has implications for endostatin function. We conclude that zinc is likely to play a structural rather than a critical functional role in endostatin. Variable zinc coordination in endostatin.,Hohenester E, Sasaki T, Mann K, Timpl R J Mol Biol. 2000 Mar 17;297(1):1-6. PMID:10704302[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
This page was last modified 23:54, 20 November 2024.