PDBsum entry 5e9c

Hydrolase

PDB id: 5e9c

Contents

Protein chains

385 a.a.

74 a.a.

Ligands

5KV-IDR-SGN-UAP

NAG ×3

SO4

Metals

_CL

Waters ×224

PDB id:

5e9c

Name:

Hydrolase

Title:

Crystal structure of human heparanase in complex with heparin tetrasaccharide dp4

Structure:

Heparanase. Chain: a. Fragment: residues 158-543. Synonym: endo-glucoronidase,heparanase-1,hpa1. Engineered: yes. Heparanase. Chain: b. Fragment: residues 36-109. Synonym: endo-glucoronidase,heparanase-1,hpa1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hpse, hep, hpa, hpa1, hpr1, hpse1, hse1. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_taxid: 7111

Resolution:

1.73Å R-factor: 0.174 R-free: 0.211

Authors:

L.Wu,G.J.Davies

Key ref:

L.Wu et al. (2015). Structural characterization of human heparanase reveals insights into substrate recognition. Nat Struct Biol, 22, 1016-1022. PubMed id: 26575439 DOI: 10.1038/nsmb.3136

Date:

15-Oct-15 Release date: 18-Nov-15

Protein chain

Q9Y251  (HPSE_HUMAN) -  Heparanase from Homo sapiens

Seq: 543 a.a.

Struc: 385 a.a.*

Protein chain

Q9Y251  (HPSE_HUMAN) -  Heparanase from Homo sapiens

Seq: 543 a.a.

Struc: 74 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.2.1.166 - heparanase.

DOI no: 10.1038/nsmb.3136

Nat Struct Biol 22:1016-1022 (2015)

PubMed id: 26575439

Structural characterization of human heparanase reveals insights into substrate recognition.

L.Wu, C.M.Viola, A.M.Brzozowski, G.J.Davies.

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-β-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-Å to 1.9-Å 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.