1bnl

ZINC DEPENDENT DIMERS OBSERVED IN CRYSTALS OF HUMAN ENDOSTATINZINC DEPENDENT DIMERS OBSERVED IN CRYSTALS OF HUMAN ENDOSTATIN

Structural highlights

1bnl is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

COIA1_HUMAN Defects in COL18A1 are a cause of Knobloch syndrome type 1 (KNO1) [MIM:267750. An autosomal recessive disorder defined by the occurrence of high myopia, vitreoretinal degeneration with retinal detachment, macular abnormalities and occipital encephalocele.^[1]

Function

COIA1_HUMAN COLA18A probably plays a major role in determining the retinal structure as well as in the closure of the neural tube. 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 PubMed

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.

Zinc-dependent dimers observed in crystals of human endostatin.,Ding YH, Javaherian K, Lo KM, Chopra R, Boehm T, Lanciotti J, Harris BA, Li Y, Shapiro R, Hohenester E, Timpl R, Folkman J, Wiley DC Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10443-8. PMID:9724722^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sertie AL, Sossi V, Camargo AA, Zatz M, Brahe C, Passos-Bueno MR. Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome). Hum Mol Genet. 2000 Aug 12;9(13):2051-8. PMID:10942434
↑ Ding YH, Javaherian K, Lo KM, Chopra R, Boehm T, Lanciotti J, Harris BA, Li Y, Shapiro R, Hohenester E, Timpl R, Folkman J, Wiley DC. Zinc-dependent dimers observed in crystals of human endostatin. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10443-8. PMID:9724722

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OCA

[1] Sertie AL, Sossi V, Camargo AA, Zatz M, Brahe C, Passos-Bueno MR. Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome). Hum Mol Genet. 2000 Aug 12;9(13):2051-8. PMID:10942434

[2] Ding YH, Javaherian K, Lo KM, Chopra R, Boehm T, Lanciotti J, Harris BA, Li Y, Shapiro R, Hohenester E, Timpl R, Folkman J, Wiley DC. Zinc-dependent dimers observed in crystals of human endostatin. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10443-8. PMID:9724722

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