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PDBsum entry 2c3f

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protein metals links
Lyase PDB id
2c3f
Jmol
Contents
Protein chain
322 a.a. *
Metals
_NA ×2
Waters ×264
* Residue conservation analysis
PDB id:
2c3f
Name: Lyase
Title: The structure of a group a streptococcal phage-encoded tail-fibre showing hyaluronan lyase activity.
Structure: Hyaluronidase, phage associated. Chain: a. Synonym: hylp1. Engineered: yes
Source: Streptococcus pyogenes. Organism_taxid: 1314. Strain: m1 gas sf370. Atcc: 700294. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Biol. unit: Trimer (from PDB file)
Resolution:
1.81Å     R-factor:   0.190     R-free:   0.223
Authors: E.J.Taylor,N.L.Smith,A.-M.Linsay,S.J.Charnock, J.P.Turkenburg,E.J.Dodson,G.J.Davies,G.W.Black
Key ref:
N.L.Smith et al. (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. PubMed id: 16314578 DOI: 10.1073/pnas.0504782102
Date:
06-Oct-05     Release date:   29-Nov-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9A0M7  (Q9A0M7_STRP1) -  Hyaluronidase, phage associated
Seq:
Struc:
337 a.a.
322 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     capsule polysaccharide biosynthetic process   1 term 
  Biochemical function     hyalurononglucosaminidase activity     1 term  

 

 
DOI no: 10.1073/pnas.0504782102 Proc Natl Acad Sci U S A 102:17652-17657 (2005)
PubMed id: 16314578  
 
 
Structure of a group A streptococcal phage-encoded virulence factor reveals a catalytically active triple-stranded beta-helix.
N.L.Smith, E.J.Taylor, A.M.Lindsay, S.J.Charnock, J.P.Turkenburg, E.J.Dodson, G.J.Davies, G.W.Black.
 
  ABSTRACT  
 
Streptococcus pyogenes (group A Streptococcus) causes severe invasive infections including scarlet fever, pharyngitis (streptococcal sore throat), skin infections, necrotizing fasciitis (flesh-eating disease), septicemia, erysipelas, cellulitis, acute rheumatic fever, and toxic shock. The conversion from nonpathogenic to toxigenic strains of S. pyogenes is frequently mediated by bacteriophage infection. One of the key bacteriophage-encoded virulence factors is a putative "hyaluronidase," HylP1, a phage tail-fiber protein responsible for the digestion of the S. pyogenes hyaluronan capsule during phage infection. Here we demonstrate that HylP1 is a hyaluronate lyase. The 3D structure, at 1.8-angstroms resolution, reveals an unusual triple-stranded beta-helical structure and provides insight into the structural basis for phage tail assembly and the role of phage tail proteins in virulence. Unlike the triple-stranded beta-helix assemblies of the bacteriophage T4 injection machinery and the tailspike endosialidase of the Escherichia coli K1 bacteriophage K1F, HylP1 possesses three copies of the active center on the triple-helical fiber itself without the need for an accessory catalytic domain. The triple-stranded beta-helix is not simply a structural scaffold, as previously envisaged; it is harnessed to provide a 200-angstroms-long substrate-binding groove for the optimal reduction in hyaluronan viscosity to aid phage penetration of the capsule.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. The 3D structure of HylP1. (a) Divergent (wall-eyed) stereoview of HylP1 colored according to chain with the Asp-137/Tyr-149 couple shown in cpk representation (yellow). (b) The TS Hs of the bacteriophage T4 gp5 and gp12 proteins and the E. coli K1 bacteriophage poly(2,8-sialidase). HylP1 is unique in possessing catalytic activity within the TS H itself, in marked contrast to the appended catalytic lysozyme and sialidase of the bacteriophage T4 and E. coli K1 bacteriophage proteins. (c) Close-up of the Asp-137/Tyr-149 pair whose mutation renders HylP1 inactive while still maintaining structural integrity. These images were drawn with MOLSCRIPT (43) and BOBSCRIPT (30).
Figure 4.
Fig. 4. The substrate-binding groove of HylP1. (Upper) Electrostatic surface potential of HylP1 (in divergent stereo) revealing an extended substrate binding cleft that is predominantly positively charged, complementing the negative charge of the substrate hyaluronic acid. (Lower) Complementarity with the alternating glucuronic acid moieties of the substrate along the putative substrate groove is provided by a "barber's pole" of positively charged residues (colored blue) including Arg-163, -190, -216, -277, and -279 and Lys-117, -119, -166, -176, and -226. Asp-137 and Tyr-149 are colored red and green, respectively. This figure was drawn with PYMOL (http://pymol.sourceforge.net).
 
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21330133 E.C.Schulz, and R.Ficner (2011).
Knitting and snipping: chaperones in β-helix folding.
  Curr Opin Struct Biol, 21, 232-239.  
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
20805221 M.L.Garron, and M.Cygler (2010).
Structural and mechanistic classification of uronic acid-containing polysaccharide lyases.
  Glycobiology, 20, 1547-1573.  
  21129200 P.G.Leiman, F.Arisaka, M.J.van Raaij, V.A.Kostyuchenko, A.A.Aksyuk, S.Kanamaru, and M.G.Rossmann (2010).
Morphogenesis of the T4 tail and tail fibers.
  Virol J, 7, 355.  
20552664 T.V.Vuong, and D.B.Wilson (2010).
Glycoside hydrolases: catalytic base/nucleophile diversity.
  Biotechnol Bioeng, 107, 195-205.  
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.  
19438710 P.Mishra, R.Prem Kumar, A.S.Ethayathulla, N.Singh, S.Sharma, M.Perbandt, C.Betzel, P.Kaur, A.Srinivasan, V.Bhakuni, and T.P.Singh (2009).
Polysaccharide binding sites in hyaluronate lyase--crystal structures of native phage-encoded hyaluronate lyase and its complexes with ascorbic acid and lactose.
  FEBS J, 276, 3392-3402.
PDB codes: 2yw0 3eka
18547389 S.Barbirz, J.J.Müller, C.Uetrecht, A.J.Clark, U.Heinemann, and R.Seckler (2008).
Crystal structure of Escherichia coli phage HK620 tailspike: podoviral tailspike endoglycosidase modules are evolutionarily related.
  Mol Microbiol, 69, 303-316.
PDB codes: 2vji 2vjj
17407184 M.Zhang, F.M.McDonald, S.S.Sturrock, S.J.Charnock, I.Humphery-Smith, and G.W.Black (2007).
Group A streptococcus cell-associated pathogenic proteins as revealed by growth in hyaluronic acid-enriched media.
  Proteomics, 7, 1379-1390.  
  17355641 P.Serwer (2007).
Evolution and the complexity of bacteriophages.
  Virol J, 4, 30.  
16522010 R.Stern, and M.J.Jedrzejas (2006).
Hyaluronidases: their genomics, structures, and mechanisms of action.
  Chem Rev, 106, 818-839.  
16495121 V.L.Yip, and S.G.Withers (2006).
Breakdown of oligosaccharides by the process of elimination.
  Curr Opin Chem Biol, 10, 147-155.  
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.