PDBsum entry 1cb8

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Lyase PDB id
Protein chain
675 a.a. *
Waters ×526
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Chondroitinase ac lyase from flavobacterium heparinum
Structure: Protein (chondroitinase ac). Chain: a. Ec:
Source: Pedobacter heparinus. Organism_taxid: 984. Cellular_location: intracellular
1.90Å     R-factor:   0.195     R-free:   0.260
Authors: J.Fethiere,B.Eggimann,M.Cygler
Key ref:
J.Féthière et al. (1999). Crystal structure of chondroitin AC lyase, a representative of a family of glycosaminoglycan degrading enzymes. J Mol Biol, 288, 635-647. PubMed id: 10329169 DOI: 10.1006/jmbi.1999.2698
02-Mar-99     Release date:   14-May-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q59288  (CSLA_PEDHD) -  Chondroitinase-AC
700 a.a.
675 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Chondroitin Ac lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Eliminative degradation of polysaccharides containing 1,4-beta-D- hexosaminyl and 1,3-beta-D-glucuronosyl linkages to disaccharides containing 4-deoxy-beta-D-gluc-4-enuronosyl groups.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     carbohydrate metabolic process   1 term 
  Biochemical function     catalytic activity     6 terms  


DOI no: 10.1006/jmbi.1999.2698 J Mol Biol 288:635-647 (1999)
PubMed id: 10329169  
Crystal structure of chondroitin AC lyase, a representative of a family of glycosaminoglycan degrading enzymes.
J.Féthière, B.Eggimann, M.Cygler.
Glycosaminoglycans (GAGs), highly sulfated polymers built of hexosamine-uronic acid disaccharide units, are major components of the extracellular matrix, mostly in the form of proteoglycans. They interact with a large array of proteins, in particular of the blood coagulation cascade. Degradation of GAGs in mammalian systems occurs by the action of GAG hydrolases. Bacteria express a large number of GAG-degrading lyases that break the hexosamine-uronic acid bond to create an unsaturated sugar ring. Flavobacterium heparinum produces at least five GAG lyases of different specificity. Chondroitin AC lyase (chondroitinase AC, 75 kDa) is highly active toward chondroitin 4-sulfate and chondroitin-6 sulfate. Its crystal structure has been determined to 1.9 A resolution. The enzyme is composed of two domains. The N-terminal domain of approximately 300 residues contains mostly alpha-helices which form a doubly-layered horseshoe (a subset of the (alpha/alpha)6 toroidal topology). The approximately 370 residues long C-terminal domain is made of beta-strands arranged in a four layered beta-sheet sandwich, with the first two sheets having nine strands each. This fold is novel and has no counterpart in full among known structures. The sequence of chondroitinase AC shows low level of homology to several hyaluronate lyases, which likely share its fold. The shape of the molecule, distribution of electrostatic potential, the pattern of conservation of the amino acids and the results of mutagenesis of hyaluronate lyases, indicate that the enzymatic activity resides primarily within the N-terminal domain. The most likely candidate for the catalytic base is His225. Other residues involved in catalysis and/or substrate binding are Arg288, Arg292, Lys298 and Lys299.
  Selected figure(s)  
Figure 5.
Figure 5. The pentagonal bipyramidal coordination of the Ca 2+ . Asp416 and Wat702 are in axial positions. Ca+2 is shown in orange, oxygen atoms in red, nitrogen atoms in blue. The residues involved in coordination are shown in full. The loop around calcium is shown as a C a trace. The magenta arrow indicates the short central b-strand of the sheet S1. Figure prepared with Raster3D (Merritt & Bacon, 1997).
Figure 6.
Figure 6. The electron density extending from the side-chain of Ser455. Modeled carbohydrate is shown in thick lines.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 288, 635-647) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20862579 B.Ustün, K.B.Sanders, P.Dani, and E.R.Kellenbach (2011).
Quantification of chondroitin sulfate and dermatan sulfate in danaparoid sodium by (1)H NMR spectroscopy and PLS regression.
  Anal Bioanal Chem, 399, 629-634.  
20805221 M.L.Garron, and M.Cygler (2010).
Structural and mechanistic classification of uronic acid-containing polysaccharide lyases.
  Glycobiology, 20, 1547-1573.  
18849565 V.Prabhakar, I.Capila, V.Soundararajan, R.Raman, and R.Sasisekharan (2009).
Recombinant Expression, Purification, and Biochemical Characterization of Chondroitinase ABC II from Proteus vulgaris.
  J Biol Chem, 284, 974-982.  
18992215 Z.Zhang, Y.Park, M.M.Kemp, W.Zhao, A.R.Im, D.Shaya, M.Cygler, Y.S.Kim, and R.J.Linhardt (2009).
Liquid chromatography-mass spectrometry to study chondroitin lyase action pattern.
  Anal Biochem, 385, 57-64.  
18093969 D.C.Oliver, and M.Paetzel (2008).
Crystal structure of the major periplasmic domain of the bacterial membrane protein assembly facilitator YidC.
  J Biol Chem, 283, 5208-5216.
PDB code: 3blc
17947240 A.Ochiai, T.Itoh, Y.Maruyama, A.Kawamata, B.Mikami, W.Hashimoto, and K.Murata (2007).
  J Biol Chem, 282, 37134-37145.
PDB codes: 2z8r 2z8s
16521140 C.S.Rye, A.Matte, M.Cygler, and S.G.Withers (2006).
An atypical approach identifies TYR234 as the key base catalyst in chondroitin AC lyase.
  Chembiochem, 7, 631-637.  
16565082 D.Shaya, A.Tocilj, Y.Li, J.Myette, G.Venkataraman, R.Sasisekharan, and M.Cygler (2006).
Crystal structure of heparinase II from Pedobacter heparinus and its complex with a disaccharide product.
  J Biol Chem, 281, 15525-15535.
PDB codes: 2fuq 2fut
16854993 M.S.Akhtar, M.Y.Krishnan, and V.Bhakuni (2006).
Insights into the mechanism of action of hyaluronate lyase: role of C-terminal domain and Ca2+ in the functional regulation of enzyme.
  J Biol Chem, 281, 28336-28344.  
16834555 R.Sasisekharan, R.Raman, and V.Prabhakar (2006).
Glycomics approach to structure-function relationships of glycosaminoglycans.
  Annu Rev Biomed Eng, 8, 181-231.  
16893885 T.Itoh, W.Hashimoto, B.Mikami, and K.Murata (2006).
Crystal structure of unsaturated glucuronyl hydrolase complexed with substrate: molecular insights into its catalytic reaction mechanism.
  J Biol Chem, 281, 29807-29816.
PDB codes: 2ahf 2ahg 2d5j
15155751 G.Michel, K.Pojasek, Y.Li, T.Sulea, R.J.Linhardt, R.Raman, V.Prabhakar, R.Sasisekharan, and M.Cygler (2004).
The structure of chondroitin B lyase complexed with glycosaminoglycan oligosaccharides unravels a calcium-dependent catalytic machinery.
  J Biol Chem, 279, 32882-32896.
PDB codes: 1ofl 1ofm
15148314 T.Itoh, S.Akao, W.Hashimoto, B.Mikami, and K.Murata (2004).
Crystal structure of unsaturated glucuronyl hydrolase, responsible for the degradation of glycosaminoglycan, from Bacillus sp. GL1 at 1.8 A resolution.
  J Biol Chem, 279, 31804-31812.
PDB code: 1vd5
15180986 Z.Wei, P.Zhang, Z.Zhou, Z.Cheng, M.Wan, and W.Gong (2004).
Crystal structure of human eIF3k, the first structure of eIF3 subunits.
  J Biol Chem, 279, 34983-34990.
PDB code: 1rz4
14523022 D.J.Rigden, and M.J.Jedrzejas (2003).
Structures of Streptococcus pneumoniae hyaluronate lyase in complex with chondroitin and chondroitin sulfate disaccharides. Insights into specificity and mechanism of action.
  J Biol Chem, 278, 50596-50606.
PDB codes: 1ojm 1ojn 1ojo 1ojp
12923184 H.M.Holden, I.Rayment, and J.B.Thoden (2003).
Structure and function of enzymes of the Leloir pathway for galactose metabolism.
  J Biol Chem, 278, 43885-43888.  
12717027 J.B.Thoden, J.Kim, F.M.Raushel, and H.M.Holden (2003).
The catalytic mechanism of galactose mutarotase.
  Protein Sci, 12, 1051-1059.
PDB codes: 1ns0 1ns2 1ns4 1ns7 1ns8 1nsm 1nsr 1nss 1nsu 1nsv 1nsx 1nsz
12719417 M.S.Akhtar, and V.Bhakuni (2003).
Streptococcus pneumoniae hyaluronate lyase contains two non-cooperative independent folding/unfolding structural domains: characterization of functional domain and inhibitors of enzyme.
  J Biol Chem, 278, 25509-25516.  
15224891 P.Michaud, A.Da Costa, B.Courtois, and J.Courtois (2003).
Polysaccharide lyases: recent developments as biotechnological tools.
  Crit Rev Biotechnol, 23, 233-266.  
12029040 F.Blain, A.L.Tkalec, Z.Shao, C.Poulin, M.Pedneault, K.Gu, B.Eggimann, J.Zimmermann, and H.Su (2002).
Expression system for high levels of GAG lyase gene expression and study of the hepA upstream region in Flavobacterium heparinum.
  J Bacteriol, 184, 3242-3252.  
11907040 J.B.Thoden, and H.M.Holden (2002).
High resolution X-ray structure of galactose mutarotase from Lactococcus lactis.
  J Biol Chem, 277, 20854-20861.
PDB codes: 1l7j 1l7k
12218067 J.B.Thoden, J.Kim, F.M.Raushel, and H.M.Holden (2002).
Structural and kinetic studies of sugar binding to galactose mutarotase from Lactococcus lactis.
  J Biol Chem, 277, 45458-45465.
PDB codes: 1mmu 1mmx 1mmy 1mmz 1mn0
11157235 W.Hashimoto, H.Miki, N.Tsuchiya, H.Nankai, and K.Murata (2001).
Polysaccharide lyase: molecular cloning, sequencing, and overexpression of the xanthan lyase gene of Bacillus sp. strain GL1.
  Appl Environ Microbiol, 67, 713-720.  
10813837 D.G.Pritchard, J.O.Trent, X.Li, P.Zhang, M.L.Egan, and J.R.Baker (2000).
Characterization of the active site of group B streptococcal hyaluronan lyase.
  Proteins, 40, 126-134.  
10716923 S.Li, S.J.Kelly, E.Lamani, M.Ferraroni, and M.J.Jedrzejas (2000).
Structural basis of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase.
  EMBO J, 19, 1228-1240.
PDB code: 1egu
10930840 W.Huang, A.Matte, S.Suzuki, N.Sugiura, H.Miyazono, and M.Cygler (2000).
Crystallization and preliminary X-ray analysis of chondroitin sulfate ABC lyases I and II from Proteus vulgaris.
  Acta Crystallogr D Biol Crystallogr, 56, 904-906.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.