PDBsum entry 1c82

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protein ligands metals links
Lyase PDB id
Protein chain
719 a.a. *
CAC ×2
_NA ×2
Waters ×573
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Mechanism of hyaluronan binding and degradation: structure o streptococcus pneumoniae hyaluronate lyase in complex with acid disaccharide at 1.7 a resolution
Structure: Hyaluronate lyase. Chain: a. Engineered: yes
Source: Streptococcus pneumoniae. Organism_taxid: 1313. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Other_details: escherichia coli
1.70Å     R-factor:   0.215     R-free:   0.257
Authors: K.Ponnuraj,M.J.Jedrzejas
Key ref:
K.Ponnuraj and M.J.Jedrzejas (2000). Mechanism of hyaluronan binding and degradation: structure of Streptococcus pneumoniae hyaluronate lyase in complex with hyaluronic acid disaccharide at 1.7 A resolution. J Mol Biol, 299, 885-895. PubMed id: 10843845 DOI: 10.1006/jmbi.2000.3817
05-Apr-00     Release date:   05-Apr-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q54873  (HYSA_STRPN) -  Hyaluronate lyase
1066 a.a.
719 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 8 residue positions (black crosses)

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

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: 10.1006/jmbi.2000.3817 J Mol Biol 299:885-895 (2000)
PubMed id: 10843845  
Mechanism of hyaluronan binding and degradation: structure of Streptococcus pneumoniae hyaluronate lyase in complex with hyaluronic acid disaccharide at 1.7 A resolution.
K.Ponnuraj, M.J.Jedrzejas.
Hyaluronic acid (HA) is an important constituent of the extracellular matrix; its bacterial degradation has been postulated to contribute to the spread of certain streptococci through tissue. Pneumococci and other streptococci produce hyaluronate lyase, an enzyme which depolymerizes HA, thus hyaluronate lyase might contribute directly to bacterial invasion. Although two different mechanisms for lyase action have been proposed, there was no crystallographic evidence to support those mechanisms. Here, we report the high-resolution crystal structure of Streptococcus pneumoniae hyaluronate lyase in the presence of HA disaccharide product, which ultimately provides the first crystallographic evidence for the binding of HA to hyaluronate lyase. This structural complex revealed a key interaction between the Streptococcus peneumoniae hyaluronate lyase protein and the product, and supports our previously proposed novel catalytic mechanism for HA degradation based on the native Streptococcus peneumoniae hyaluronate lyase structure. The information provided by this complex structure will likely be useful in the development of antimicrobial pharmaceutical agents.
  Selected figure(s)  
Figure 2.
Figure 2. (a) Stereo view of the 2F[o] -F[c] electron density map for (I) HA1 (II) HA2. The contour level is 1.0 s and the Figure was prepared with CHAIN [Sack and Quiocho 1997]. HA1 and HA2 adopt different conformations. The stacking interaction between the sugar ring of glucosamine of HA1 with Trp292 is the major reason for the differences in the conformations of HA1 and HA2. In HA2, the sugar ring of glucosamine does not involve any stacking interaction. Detailed interactions are shown in (c) and (d). (b) Electrostatic surface potential representation of a part of the carbohydrate-binding cleft in SpnHL with bound product HA1. The highly positively charged region is represented in blue. Product HA1 is shown in ball-and-stick form. The Figure was prepared with the program RIBBONS [Carson 1997]. (c) Stereo view of a detailed hydrogen bond/van der Waals interactions between the SpnHL protein and the product HA1. Contact interactions are represented by broken lines. The key interaction between Oy Tyr408 and the O4 atom of N-acetyl glucosamine is shown in thick red broken lines. (d) Stereo diagram representing a detailed hydrogen bond/van der Waals interactions between the SpnHL protein and the product HA2. Contact interactions are shown as broken lines.
Figure 3.
Figure 3. (a) Stereo diagram showing the spatial orientation of bound products HA1 and HA2 (both in blue) with reoriented HA2 (red). The interactions between the catalytic residues and the products are shown by broken lines. The Figure was prepared with the program RIBBONS [Carson 1997]. (b) Schematic of HA degradation mechanism. (I) Asn349 interacts with carboxylate of glucoronic acid, Tyr408 is hydrogen bonded to the glycosidic oxygen atom (O4) and His399 is closely positioned to C5 of the glucuronic acid moiety. (II) His399 extracts the proton at C5 on the glucuronic acid, resulting in the formation of a double bond between C4 and C5. (III) Tyr408 provides a proton to the glycosidic oxygen, resulting in cleavage of the glycosidic bond.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 299, 885-895) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21287626 Z.H.Elmabrouk, F.Vincent, M.Zhang, N.L.Smith, J.P.Turkenburg, S.J.Charnock, G.W.Black, and E.J.Taylor (2011).
Crystal structures of a family 8 polysaccharide lyase reveal open and highly occluded substrate-binding cleft conformations.
  Proteins, 79, 965-974.
PDB codes: 2wco 2wda 2x03
19089975 H.V.Joshi, M.J.Jedrzejas, and Groot (2009).
Domain motions of hyaluronan lyase underlying processive hyaluronan translocation.
  Proteins, 76, 30-46.  
18366340 J.A.Preston, and D.H.Dockrell (2008).
Virulence factors in pneumococcal respiratory pathogenesis.
  Future Microbiol, 3, 205-221.  
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.  
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.  
16245359 K.Kemparaju, and K.S.Girish (2006).
Snake venom hyaluronidase: a therapeutic target.
  Cell Biochem Funct, 24, 7.  
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.  
16415347 P.Mishra, M.S.Akhtar, and V.Bhakuni (2006).
Unusual structural features of the bacteriophage-associated hyaluronate lyase (hylp2).
  J Biol Chem, 281, 7143-7150.  
16522010 R.Stern, and M.J.Jedrzejas (2006).
Hyaluronidases: their genomics, structures, and mechanisms of action.
  Chem Rev, 106, 818-839.  
15718240 C.D.Blundell, A.Almond, D.J.Mahoney, P.L.DeAngelis, I.D.Campbell, and A.J.Day (2005).
Towards a structure for a TSG-6.hyaluronan complex by modeling and NMR spectroscopy: insights into other members of the link module superfamily.
  J Biol Chem, 280, 18189-18201.  
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.  
15175306 D.R.Brown, L.A.Zacher, and W.G.Farmerie (2004).
Spreading factors of Mycoplasma alligatoris, a flesh-eating mycoplasma.
  J Bacteriol, 186, 3922-3927.  
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
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
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.  
12446724 M.Nukui, K.B.Taylor, D.T.McPherson, M.K.Shigenaga, and M.J.Jedrzejas (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.
PDB codes: 1n7n 1n7o 1n7p 1n7q 1n7r
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.  
12475987 W.Hashimoto, H.Nankai, B.Mikami, and K.Murata (2003).
Crystal structure of Bacillus sp. GL1 xanthan lyase, which acts on the side chains of xanthan.
  J Biol Chem, 278, 7663-7673.
PDB codes: 1j0m 1j0n
11717315 A.J.Day, and G.D.Prestwich (2002).
Hyaluronan-binding proteins: tying up the giant.
  J Biol Chem, 277, 4585-4588.  
12130645 L.V.Mello, B.L.De Groot, S.Li, and M.J.Jedrzejas (2002).
Structure and flexibility of Streptococcus agalactiae hyaluronate lyase complex with its substrate. Insights into the mechanism of processive degradation of hyaluronan.
  J Biol Chem, 277, 36678-36688.
PDB code: 1lxm
11785764 A.J.Day, and J.K.Sheehan (2001).
Hyaluronan: polysaccharide chaos to protein organisation.
  Curr Opin Struct Biol, 11, 617-622.  
11381099 M.J.Jedrzejas (2001).
Pneumococcal virulence factors: structure and function.
  Microbiol Mol Biol Rev, 65, 187.  
11327856 W.Huang, L.Boju, L.Tkalec, H.Su, H.O.Yang, N.S.Gunay, R.J.Linhardt, Y.S.Kim, A.Matte, and M.Cygler (2001).
Active site of chondroitin AC lyase revealed by the structure of enzyme-oligosaccharide complexes and mutagenesis.
  Biochemistry, 40, 2359-2372.
PDB codes: 1hm2 1hm3 1hmu 1hmw
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 codes are shown on the right.