5E9B: Crystal Structure Of Human Heparanase In Complex With Hepmer M09s05a

Citation:
Abstract
Heparan sulfate (HS) is a glycosaminoglycan that forms a key component of the extracellular matrix (ECM). Breakdown of HS is carried out by heparanase (HPSE), an endo-beta-glucuronidase of the glycoside hydrolase 79 (GH79) family. Overexpression of HPSE results in breakdown of extracellular HS and release of stored growth factors and hence is strongly linked to cancer metastasis. Here we present crystal structures of human HPSE at 1.6-A to 1.9-A resolution that reveal how an endo-acting binding cleft is exposed by proteolytic activation of latent proHPSE. We used oligosaccharide complexes to map the substrate-binding and sulfate-recognition motifs. These data shed light on the structure and interactions of a key enzyme involved in ECM maintenance and provide a starting point for the design of HPSE inhibitors for use as biochemical tools and anticancer therapeutics.
PDB ID: 5E9BDownload
MMDB ID: 134320
PDB Deposition Date: 2015/10/14
Updated in MMDB: 2015/12
Experimental Method:
x-ray diffraction
Resolution: 1.88  Å
Source Organism:
Similar Structures:
Biological Unit for 5E9B: dimeric; determined by software (PISA)
Molecular Components in 5E9B
Label Count Molecule
Proteins (2 molecules)
1
Heparanase(Gene symbol: HPSE)
Molecule annotation
1
Heparanase(Gene symbol: HPSE)
Molecule annotation
Chemicals (8 molecules)
1
3
2
1
3
2
4
1
5
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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