Structural highlights
Function
[CABC_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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Chondroitin Sulfate ABC lyase I from Proteus vulgaris is an endolytic, broad-specificity glycosaminoglycan lyase, which degrades chondroitin, chondroitin-4-sulfate, dermatan sulfate, chondroitin-6-sulfate, and hyaluronan by beta-elimination of 1,4-hexosaminidic bond to unsaturated disaccharides and tetrasaccharides. Its structure revealed three domains. The N-terminal domain has a fold similar to that of carbohydrate-binding domains of xylanases and some lectins, the middle and C-terminal domains are similar to the structures of the two-domain chondroitin lyase AC and bacterial hyaluronidases. Although the middle domain shows a very low level of sequence identity with the catalytic domains of chondroitinase AC and hyaluronidase, the residues implicated in catalysis of the latter enzymes are present in chondroitinase ABC I. The substrate-binding site in chondroitinase ABC I is in a wide-open cleft, consistent with the endolytic action pattern of this enzyme. The tryptophan residues crucial for substrate binding in chondroitinase AC and hyaluronidases are lacking in chondroitinase ABC I. The structure of chondroitinase ABC I provides a framework for probing specific functions of active-site residues for understanding the remarkably broad specificity of this enzyme and perhaps engineering a desired specificity. The electron density map showed clearly that the deposited DNA sequence for residues 495-530 of chondroitin ABC lyase I, the segment containing two putative active-site residues, contains a frame-shift error resulting in an incorrectly translated amino acid sequence.
Crystal structure of Proteus vulgaris chondroitin sulfate ABC lyase I at 1.9A resolution.,Huang W, Lunin VV, Li Y, Suzuki S, Sugiura N, Miyazono H, Cygler M J Mol Biol. 2003 May 2;328(3):623-34. PMID:12706721[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ Huang W, Lunin VV, Li Y, Suzuki S, Sugiura N, Miyazono H, Cygler M. Crystal structure of Proteus vulgaris chondroitin sulfate ABC lyase I at 1.9A resolution. J Mol Biol. 2003 May 2;328(3):623-34. PMID:12706721
