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PDBsum entry 1f1s

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protein links
Lyase PDB id
1f1s
Jmol
Contents
Protein chain
814 a.a. *
Waters ×538
* Residue conservation analysis
PDB id:
1f1s
Name: Lyase
Title: Crystal structure of streptococcus agalactiae hyaluronate lyase at 2.1 angstrom resolution.
Structure: Hyaluronate lyase. Chain: a. Fragment: sequence from 171 to 984. Engineered: yes
Source: Streptococcus agalactiae. Organism_taxid: 1311. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.10Å     R-factor:   0.191     R-free:   0.253
Authors: S.Li,M.J.Jedrzejas
Key ref:
S.Li and M.J.Jedrzejas (2001). Hyaluronan binding and degradation by Streptococcus agalactiae hyaluronate lyase. J Biol Chem, 276, 41407-41416. PubMed id: 11527972 DOI: 10.1074/jbc.M106634200
Date:
19-May-00     Release date:   16-Jan-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q53591  (HYSA_STRA3) -  Hyaluronate lyase
Seq:
Struc:
 
Seq:
Struc:
984 a.a.
814 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 15 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.4.2.2.1  - Hyaluronate lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hyaluronate = N 3-(4-deoxy-beta-D-gluc-4-enuronosyl)-N-acetyl-D- glucosamine

= N
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     carbohydrate metabolic process   1 term 
  Biochemical function     catalytic activity     4 terms  

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.M106634200 J Biol Chem 276:41407-41416 (2001)
PubMed id: 11527972  
 
 
Hyaluronan binding and degradation by Streptococcus agalactiae hyaluronate lyase.
S.Li, M.J.Jedrzejas.
 
  ABSTRACT  
 
Streptococcus agalactiae hyaluronate lyase is a virulence factor that helps this pathogen to break through the biophysical barrier of the host tissues by the enzymatic degradation of hyaluronan and certain chondroitin sulfates at beta-1,4 glycosidic linkages. Crystal structures of the native enzyme and the enzyme-product complex were determined at 2.1- and 2.2-A resolutions, respectively. An elongated cleft transversing the middle of the molecule has been identified as the substrate-binding place. Two product molecules of hyaluronan degradation were observed bound to the cleft. The enzyme catalytic site was identified to comprise three residues: His(479), Tyr(488), and Asn(429). The highly positively charged cleft facilitates the binding of the negatively charged polymeric substrate chain. The matching between the aromatic patch of the enzyme and the hydrophobic patch of the substrate chain anchors the substrate chain into degradation position. A pair of proton exchanges between the enzyme and the substrate results in the cleavage of the beta-1,4 glycosidic linkage of the substrate chain and the unsaturation of the product. Phe(423) likely determines the size of the product at the product release side of the catalytic region. Hyaluronan chain is processively degraded from the reducing end toward the nonreducing end. The unsulfated or 6-sulfated regions of chondroitin sulfate can also be degraded in the same manner as hyaluronan.
 
  Selected figure(s)  
 
Figure 5.
Fig. 5. Schematic diagram of hyaluronan degradation. The catalytic residues and their relative position to the substrate and the positions of the HA1 and HA2 disaccharides are shown schematically to illustrate the mechanism of HA degradation by SagHL as described in the text under the section "Proposed Mechanism of Hyaluronan Degradation."
Figure 6.
Fig. 6. Electrostatic potential distribution in the catalytic cleft. The cleft is placed in the same orientation as in Figs. 1-4. The positive potential is shown in blue and negative potential in red. Majority of the cleft is highly positively charged, whereas at the product-releasing end of the cleft (HA1 position) a negative patch is clearly present as labeled. The position of the hydrophobic patch is also labeled. The figure was made using Grasp (41).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 41407-41416) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20805221 M.L.Garron, and M.Cygler (2010).
Structural and mechanistic classification of uronic acid-containing polysaccharide lyases.
  Glycobiology, 20, 1547-1573.  
19089975 H.V.Joshi, M.J.Jedrzejas, and B.L.de Groot (2009).
Domain motions of hyaluronan lyase underlying processive hyaluronan translocation.
  Proteins, 76, 30-46.  
19257847 L.Rajagopal (2009).
Understanding the regulation of Group B Streptococcal virulence factors.
  Future Microbiol, 4, 201-221.  
18256495 K.Murata, S.Kawai, B.Mikami, and W.Hashimoto (2008).
Superchannel of bacteria: biological significance and new horizons.
  Biosci Biotechnol Biochem, 72, 265-277.  
16522010 R.Stern, and M.J.Jedrzejas (2006).
Hyaluronidases: their genomics, structures, and mechanisms of action.
  Chem Rev, 106, 818-839.  
15750080 S.Sukhnanand, B.Dogan, M.O.Ayodele, R.N.Zadoks, M.P.Craver, N.B.Dumas, Y.H.Schukken, K.J.Boor, and M.Wiedmann (2005).
Molecular subtyping and characterization of bovine and human Streptococcus agalactiae isolates.
  J Clin Microbiol, 43, 1177-1186.  
15849405 W.Hashimoto, K.Momma, Y.Maruyama, M.Yamasaki, B.Mikami, and K.Murata (2005).
Structure and function of bacterial super-biosystem responsible for import and depolymerization of macromolecules.
  Biosci Biotechnol Biochem, 69, 673-692.  
15849992 M.R.Ziebell, and G.D.Prestwich (2004).
Interactions of peptide mimics of hyaluronic acid with the receptor for hyaluronan mediated motility (RHAMM).
  J Comput Aided Mol Des, 18, 597-614.  
12833544 D.J.Rigden, and M.J.Jedrzejas (2003).
Genome-based identification of a carbohydrate binding module in Streptococcus pneumoniae hyaluronate lyase.
  Proteins, 52, 203-211.  
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.