PDBsum entry 4pw2

Isomerase

PDB id: 4pw2

Contents

Protein chain

510 a.a.

Ligands

CIT

Waters ×684

PDB id:

4pw2

Name:

Isomerase

Title:

Crystal structure of d-glucuronyl c5 epimerase

Structure:

D-glucuronyl c5 epimerase b. Chain: a. Engineered: yes

Source:

Danio rerio. Leopard danio,zebra danio,zebra fish. Organism_taxid: 7955. Gene: d-glucuronyl c5-epimerase, glce, glceb. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.212 R-free: 0.244

Authors:

J.Ke,Y.Qin,X.Gu,J.S.Brunzelle,H.E.Xu,K.Ding

Key ref:

Y.Qin et al. (2015). Structural and functional study of D-glucuronyl C5-epimerase. J Biol Chem, 290, 4620-4630. PubMed id: 25568314 DOI: 10.1074/jbc.M114.602201

Date:

18-Mar-14 Release date: 14-Jan-15

Protein chain

F1QR43  (GLCEB_DANRE) -  D-glucuronyl C5-epimerase B from Danio rerio

Seq: 586 a.a.

Struc: 510 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.5.1.3.17 - heparosan-N-sulfate-glucuronate 5-epimerase.
• Reaction: [heparosan-N-sulfate](n) = [heparan-N-sulfate](n)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1074/jbc.M114.602201

J Biol Chem 290:4620-4630 (2015)

PubMed id: 25568314

Structural and functional study of D-glucuronyl C5-epimerase.

Y.Qin, J.Ke, X.Gu, J.Fang, W.Wang, Q.Cong, J.Li, J.Tan, J.S.Brunzelle, C.Zhang, Y.Jiang, K.Melcher, J.P.Li, H.E.Xu, K.Ding.

ABSTRACT

Heparan sulfate (HS) is a glycosaminoglycan present on the cell surface and in the extracellular matrix, which interacts with diverse signal molecules and is essential for many physiological processes including embryonic development, cell growth, inflammation, and blood coagulation. d-Glucuronyl C5-epimerase (Glce) is a crucial enzyme in HS synthesis, converting d-glucuronic acid to l-iduronic acid to increase HS flexibility. This modification of HS is important for protein ligand recognition. We have determined the crystal structures of Glce in apo-form (unliganded) and in complex with heparin hexasaccharide (product of Glce following O-sulfation), both in a stable dimer conformation. A Glce dimer contains two catalytic sites, each at a positively charged cleft in C-terminal α-helical domains binding one negatively charged hexasaccharide. Based on the structural and mutagenesis studies, three tyrosine residues, Tyr(468), Tyr(528), and Tyr(546), in the active site were found to be crucial for the enzymatic activity. The complex structure also reveals the mechanism of product inhibition (i.e. 2-O- and 6-O-sulfation of HS keeps the C5 carbon of l-iduronic acid away from the active-site tyrosine residues). Our structural and functional data advance understanding of the key modification in HS biosynthesis.