Crystal structure of the angiogenesis inhibitor endostatin at 1.5Aresolution
- 16 March 1998
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 17 (6), 1656-1664
- https://doi.org/10.1093/emboj/17.6.1656
Abstract
A number of extracellular proteins contain cryptic inhibitors of angiogenesis. Endostatin is a 20 kDa C‐terminal proteolytic fragment of collagen XVIII that potently inhibits endothelial cell proliferation and angiogenesis. Therapy of experimental cancer with endostatin leads to tumour dormancy and does not induce resistance. We have expressed recombinant mouse endostatin and determined its crystal structure at 1.5 Å resolution. The structure reveals a compact fold distantly related to the C‐type lectin carbohydrate recognition domain and the hyaluronan‐binding Link module. The high affinity of endostatin for heparin is explained by the presence of an extensive basic patch formed by 11 arginine residues. Endostatin may inhibit angiogenesis by binding to the heparan sulphate proteoglycans involved in growth factor signalling.Keywords
This publication has 44 references indexed in Scilit:
- Mechanisms of angiogenesisNature, 1997
- Patterns and Emerging Mechanisms of the Angiogenic Switch during TumorigenesisCell, 1996
- Heparin Structure and Interactions with Basic Fibroblast Growth FactorScience, 1996
- Phase combination and cross validation in iterated density-modification calculationsActa Crystallographica Section D-Biological Crystallography, 1996
- Identification of Three N-terminal Ends of Type XVIII Collagen Chains and Tissue-specific Differences in the Expression of the Corresponding TranscriptsJournal of Biological Chemistry, 1995
- Histidine-Rich Glycoprotein and Platelet Factor 4 Mask Heparan Sulfate Proteoglycans Recognized by Acidic and Basic Fibroblast Growth FactorBiochemistry, 1994
- Energetic Characterization of the Basic Fibroblast Growth Factor-Heparin Interaction: Identification of the Heparin Binding DomainBiochemistry, 1994
- Protein Structure Comparison by Alignment of Distance MatricesJournal of Molecular Biology, 1993
- Structure of a C-type mannose-binding protein complexed with an oligosaccharideNature, 1992
- MOLSCRIPT: a program to produce both detailed and schematic plots of protein structuresJournal of Applied Crystallography, 1991