4pxq | pdb_00004pxq

Crystal structure of D-glucuronyl C5-epimerase in complex with heparin hexasaccharide

spinqualitylabelsall models 4pxq, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4pxq is a 2 chain structure with sequence from Danio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: IDS, SGN, UAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLCEB_DANRE Converts D-glucuronic acid residues adjacent to N-sulfate sugar residues to L-iduronic acid residues, both in maturing heparan sulfate (HS) and heparin chains (PubMed:16156897, PubMed:25568314). Plays a role in dorso-ventral axis specification during early development, together with glcea, where it may potentiate signaling via the BMP pathway (PubMed:16156897). Publication Abstract from PubMed 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 (GlcA) to L-iduronic acid (IdoA) 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 alpha-helical domains binding one negatively charged hexasaccharide. Based on the structural and mutagenesis studies, three tyrosine residues, Y468, Y528, and Y546 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 IdoA away from the active-site tyrosine residues. Our structural and functional data advance understanding of the key modification regulation in HS biosynthesis. Structural and functional study of D-glucuronyl C5-epimerase.,Qin Y, Ke J, Gu X, Fang J, Wang W, Cong Q, Li J, Tan J, Brunzelle JS, Zhang C, Jiang Y, Melcher K, Li JP, Xu HE, Ding K J Biol Chem. 2015 Jan 7. pii: jbc.M114.602201. PMID:25568314 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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