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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[7eiq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Proteus_vulgaris Proteus vulgaris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EIQ FirstGlance]. <br> | | <table><tr><td colspan='2'>[[7eiq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Proteus_vulgaris Proteus vulgaris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EIQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ASG:2-DEOXY-2-ACETAMIDO-BETA-D-GALACTOSE-4-SULFATE'>ASG</scene>, <scene name='pdbligand=GCD:4,5-DEHYDRO-D-GLUCURONIC+ACID'>GCD</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Chondroitin-sulfate-ABC_endolyase Chondroitin-sulfate-ABC endolyase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.2.20 4.2.2.20] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASG:2-DEOXY-2-ACETAMIDO-BETA-D-GALACTOSE-4-SULFATE'>ASG</scene>, <scene name='pdbligand=GCD:4,5-DEHYDRO-D-GLUCURONIC+ACID'>GCD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7eiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eiq OCA], [https://pdbe.org/7eiq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eiq RCSB], [https://www.ebi.ac.uk/pdbsum/7eiq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eiq ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7eiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eiq OCA], [https://pdbe.org/7eiq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eiq RCSB], [https://www.ebi.ac.uk/pdbsum/7eiq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eiq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CABC1_PROVU 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).<ref>PMID:15691229</ref> <ref>PMID:17572406</ref> <ref>PMID:9083041</ref>
| + | [https://www.uniprot.org/uniprot/CABC1_PROVU 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).<ref>PMID:15691229</ref> <ref>PMID:17572406</ref> <ref>PMID:9083041</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chondroitin-sulfate-ABC endolyase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Proteus vulgaris]] | | [[Category: Proteus vulgaris]] |
| - | [[Category: Eguchi, T]] | + | [[Category: Eguchi T]] |
| - | [[Category: Miyanaga, A]] | + | [[Category: Miyanaga A]] |
| - | [[Category: Takashima, M]] | + | [[Category: Takashima M]] |
| - | [[Category: Carbohydrate binding]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Polysaccharide lyase family 8]]
| + | |
| Structural highlights
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).[1] [2] [3]
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Prabhakar V, Capila I, Bosques CJ, Pojasek K, Sasisekharan R. Chondroitinase ABC I from Proteus vulgaris: cloning, recombinant expression and active site identification. Biochem J. 2005 Feb 15;386(Pt 1):103-12. PMID:15691229 doi:http://dx.doi.org/10.1042/BJ20041222
- ↑ Crespo D, Asher RA, Lin R, Rhodes KE, Fawcett JW. How does chondroitinase promote functional recovery in the damaged CNS? Exp Neurol. 2007 Aug;206(2):159-71. Epub 2007 May 8. PMID:17572406 doi:http://dx.doi.org/10.1016/j.expneurol.2007.05.001
- ↑ Hamai A, Hashimoto N, Mochizuki H, Kato F, Makiguchi Y, Horie K, Suzuki S. Two distinct chondroitin sulfate ABC lyases. An endoeliminase yielding tetrasaccharides and an exoeliminase preferentially acting on oligosaccharides. J Biol Chem. 1997 Apr 4;272(14):9123-30. PMID:9083041
- ↑ Takashima M, Watanabe I, Miyanaga A, Eguchi T. Substrate specificity of Chondroitinase ABC I based on analyses of biochemical reactions and crystal structures in complex with disaccharides. Glycobiology. 2021 Aug 12. pii: 6348415. doi: 10.1093/glycob/cwab086. PMID:34392362 doi:http://dx.doi.org/10.1093/glycob/cwab086
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