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PDBsum entry 1n7q

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protein ligands links
Lyase PDB id
1n7q
Jmol
Contents
Protein chain
721 a.a. *
Ligands
NAG-BDP-NAG-BDP-
NAG-GTR
Waters ×480
* Residue conservation analysis
PDB id:
1n7q
Name: Lyase
Title: Streptococcus pneumoniae hyaluronate lyase w291a/w292a doubl complex with hyaluronan hexasacchride
Structure: Hyaluronidase. Chain: a. Synonym: hyaluronate lyase. Engineered: yes. Mutation: yes
Source: Streptococcus pneumoniae. Organism_taxid: 1313. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.30Å     R-factor:   0.174     R-free:   0.249
Authors: M.Nukui,K.B.Taylor,D.T.Mcpherson,M.Shigenaga,M.J.Jedrzejas
Key ref:
M.Nukui et al. (2003). The function of hydrophobic residues in the catalytic cleft of Streptococcus pneumoniae hyaluronate lyase. Kinetic characterization of mutant enzyme forms. J Biol Chem, 278, 3079-3088. PubMed id: 12446724 DOI: 10.1074/jbc.M204999200
Date:
16-Nov-02     Release date:   31-Dec-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q54873  (HYSA_STRPN) -  Hyaluronate lyase
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1066 a.a.
721 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 10 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
Bound ligand (Het Group name = NAG)
matches with 57.00% similarity
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.M204999200 J Biol Chem 278:3079-3088 (2003)
PubMed id: 12446724  
 
 
The function of hydrophobic residues in the catalytic cleft of Streptococcus pneumoniae hyaluronate lyase. Kinetic characterization of mutant enzyme forms.
M.Nukui, K.B.Taylor, D.T.McPherson, M.K.Shigenaga, M.J.Jedrzejas.
 
  ABSTRACT  
 
Streptococcus pneumoniae hyaluronate lyase is a surface antigen of this Gram-positive human bacterial pathogen. The primary function of this enzyme is the degradation of hyaluronan, which is a major component of the extracellular matrix of the tissues of vertebrates and of some bacteria. The enzyme degrades its substrate through a beta-elimination process called proton acceptance and donation. The inherent part of this degradation is a processive mode of action of the enzyme degrading hyaluronan into unsaturated disaccharide hyaluronic acid blocks from the reducing to the nonreducing end of the polymer following the initial random endolytic binding to the substrate. The final degradation product is the unsaturated disaccharide hyaluronic acid. The residues of the enzyme that are involved in various aspects of such degradation were identified based on the three-dimensional structures of the native enzyme and its complexes with hyaluronan substrates of various lengths. The catalytic residues were identified to be Asn(349), His(399), and Tyr(408). The residues responsible for the release of the product of the reaction were identified as Glu(388), Asp(398), and Thr(400), and they were termed negative patch. The hydrophobic residues Trp(291), Trp(292), and Phe(343) were found to be responsible for the precise positioning of the substrate for enzyme catalysis and named hydrophobic patch. The comparison of the specific activities and kinetic properties of the wild type and the mutant enzymes involving the hydrophobic patch residues W292A, F343V, W291A/W292A, W292A/F343V, and W291A/W292A/F343V allowed for the characterization of every mutant and for the correlation of the activity and kinetic properties of the enzyme with its structure as well as the mechanism of catalysis.
 
  Selected figure(s)  
 
Figure 4.
Fig. 4. Stereo diagram of the wild type and five mutant structures of hyaluronate lyase. The cleft with the region of the hydrophobic patch built from Trp292, Trp292, and Phe^343 residues (labeled) is shown. The orientation of structure in all the panels is the same. The figure was prepared with O (33). A, wild type-like enzyme complex with HA[6] (based on Protein Data Bank code 1loh) (19). B, F343V mutant. C, W292A mutant. D, W292A/F343V double mutant. E, W291A/W292A double mutant complex with HA[6]. F, W291A/W292A/F343V triple mutant complex with HA[6].
Figure 5.
Fig. 5. Proposed chemical formulation of the mechanism of S. pneumoniae hyaluronate. Only the catalytic residues, Asn349, His399, and Tyr408, and two disaccharide units, HA1 and HA2, are shown. The movement of hydrogens relevant to the catalytic process is indicated by arrows.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 3079-3088) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19202092 A.M.Lindsay, M.Zhang, Z.Mitchell, M.T.Holden, A.S.Waller, I.C.Sutcliffe, and G.W.Black (2009).
The Streptococcus equi prophage-encoded protein SEQ2045 is a hyaluronan-specific hyaluronate lyase that is produced during equine infection.
  Microbiology, 155, 443-449.  
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.  
16470658 C.L.Gatlin, R.Pieper, S.T.Huang, E.Mongodin, E.Gebregeorgis, P.P.Parmar, D.J.Clark, H.Alami, L.Papazisi, R.D.Fleischmann, S.R.Gill, and S.N.Peterson (2006).
Proteomic profiling of cell envelope-associated proteins from Staphylococcus aureus.
  Proteomics, 6, 1530-1549.  
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.  
16522010 R.Stern, and M.J.Jedrzejas (2006).
Hyaluronidases: their genomics, structures, and mechanisms of action.
  Chem Rev, 106, 818-839.  
16314578 N.L.Smith, E.J.Taylor, A.M.Lindsay, S.J.Charnock, J.P.Turkenburg, E.J.Dodson, G.J.Davies, and G.W.Black (2005).
Structure of a group A streptococcal phage-encoded virulence factor reveals a catalytically active triple-stranded beta-helix.
  Proc Natl Acad Sci U S A, 102, 17652-17657.
PDB code: 2c3f
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.  
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.