7eis

Crystal structure of chondroitin ABC lyase I in complex with chondroitin disaccharide 0S

spinqualitylabelsall models 7eis, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7eis is a 1 chain structure with sequence from Proteus vulgaris. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: GCD, MG, NGA, PRD_900058 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CABC1_PROVU Endolytic, broad-specificity glycosaminoglycan lyase, which degrades the polysaccharides chondroitin, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate and to a lesser extent hyaluronan, by beta-elimination of 1,4-hexosaminidic bond to unsaturated tetrasaccharides and disaccharides. Is not active against keratan sulfate, heparan sulfate, and heparin. Is able to promote functional recovery in the injured central nervous system (CNS), via its role in the disruption of the normal organization of the extracellular matrix (ECM). Publication Abstract from PubMed Chondroitinase ABC I (cABC-I) is the enzyme which cleaves the beta-1,4 glycosidic linkage of chondroitin sulfate (CS) by beta-elimination. To elucidate more accurately the substrate specificity of cABC-I, we evaluated the kinetic parameters of cABC-I and its reactivity with CS isomers displaying less structural heterogeneity as substrates, e.g., approximately 90 percent of disaccharide units in Chondroitin sulfate A (CSA) or Chondroitin sulfate C (CSC) is D-glucuronic acid and 4-O-sulfated N-acetyl galactosamine (GalNAc) (A-unit) or D-glucuronic acid and 6-O-sulfated GalNAc (C-unit), respectively. cABC-I showed the highest reactivity to CSA and CSC among all CS isomers, and the kcat/Km of cABC-I was higher for CSA than for CSC. Next, we determined the crystal structures of cABC-I in complex with CS disaccharides, and analyzed the crystallographic data in combination with molecular docking data. Arg500 interacts with 4-O-sulfated and 6-O-sulfated GalNAc residues. The distance between Arg500 and the 4-O-sulfate group was 0.8 A shorter than that between Arg500 and the 6-O-sulfated group. Moreover, it is likely that the 6-O-sulfated group is electrostatically repulsed by the nearby Asp490. Thus, we demonstrated that cABC-I has the highest affinity for the CSA richest in 4-O-sulfated GalNAc residues among all CS isomers. Recently, cABC-I was used to treat lumbar disc herniation. The results provide useful information to understand the mechanism of the pharmacological action of cABC-I. Substrate specificity of Chondroitinase ABC I based on analyses of biochemical reactions and crystal structures in complex with disaccharides.,Takashima M, Watanabe I, Miyanaga A, Eguchi T Glycobiology. 2021 Aug 12. pii: 6348415. doi: 10.1093/glycob/cwab086. PMID:34392362 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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