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Carbohydrate-binding module PDB id
2j44
Jmol
Contents
Protein chain
217 a.a. *
Ligands
GLC-GLC
GLC-GLC-GLC
GLC ×2
Metals
_ZN ×3
Waters ×187
* Residue conservation analysis
PDB id:
2j44
Name: Carbohydrate-binding module
Title: Alpha-glucan binding by a streptococcal virulence factor
Structure: Alkaline amylopullulanase. Chain: a. Fragment: carbohydrate-binding module, residues 135-312,314,316-353. Synonym: spndx. Engineered: yes. Other_details: tandem family 41 carbohydrate binding modules
Source: Streptococcus pneumoniae. Organism_taxid: 1313. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
2.1Å     R-factor:   0.225     R-free:   0.304
Authors: A.Lammerts Van Bueren,M.Higgins,D.Wang,R.D.Burke, A.B.Boraston
Key ref:
A.L.van Bueren et al. (2007). Identification and structural basis of binding to host lung glycogen by streptococcal virulence factors. Nat Struct Mol Biol, 14, 76-84. PubMed id: 17187076 DOI: 10.1038/nsmb1187
Date:
24-Aug-06     Release date:   11-Dec-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q97SQ7  (Q97SQ7_STRPN) -  Putative alkaline amylopullulanase
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1280 a.a.
217 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     carbohydrate metabolic process   1 term 
  Biochemical function     carbohydrate binding     1 term  

 

 
DOI no: 10.1038/nsmb1187 Nat Struct Mol Biol 14:76-84 (2007)
PubMed id: 17187076  
 
 
Identification and structural basis of binding to host lung glycogen by streptococcal virulence factors.
A.L.van Bueren, M.Higgins, D.Wang, R.D.Burke, A.B.Boraston.
 
  ABSTRACT  
 
The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basis for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal alpha-glucan-metabolizing machinery as virulence factors.
 
  Selected figure(s)  
 
Figure 2.
(a) T. maritima CBM27. (b) T. maritima CBM41. (c) SpyDX. (d) SpnDX. The following solutions were spotted on a nitrocellulose membrane: a1, amylose; a2, amylopectin; a3, pullulan; a4, dextran; a5, glycogen; b1, oat spelt xylan; b2, arabinogalactan; b3, pachyman; b4, glycerol; b5, thyroglobulin; c1, fetuin; c2, asialofetuin; c3, mucin type IS; c4, mucin type II; c5, mucin type III; d1, heparin; d2, chondroitin sulfate; d3, hyaluronic acid; d4, aggrecan; d5, proteoglycan. The ability of glycogen to interact with the nitrocellulose membrane is unknown, which may account for the weak signal produced in this experiment. 		Figure 5.
(a,b) SpnDX-1 with maltotetraose (a) and SpnDX-2 with maltotriose modeled (b). Representative electron density map (blue mesh) is a maximum likelihood^42 [A]-weighted^45 2F[o] – F[c] map contoured at 1.5 (0.30 e^- Å^-3) with phases and F[c]s derived from the final refined model. Ligand (yellow) and binding site residues (gray) are shown as sticks. (c,d) Schematics of ligand interactions with SpnDX-1 (c) and SpnDX-2 (d). (e,f) Structural overlap of the individual CBM41s, CBM41-1 (e) and CBM41-2 (f), from SpnDX (blue) and SpyDX (green). Modules are shown as C traces and conserved binding site residues are shown as sticks.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2007, 14, 76-84) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20624274 C.Frolet, M.Beniazza, L.Roux, B.Gallet, M.Noirclerc-Savoye, T.Vernet, and A.M.Di Guilmi (2010).
New adhesin functions of surface-exposed pneumococcal proteins.
  BMC Microbiol, 10, 190.  
19908036 D.Guillén, S.Sánchez, and R.Rodríguez-Sanoja (2010).
Carbohydrate-binding domains: multiplicity of biological roles.
  Appl Microbiol Biotechnol, 85, 1241-1249.  
20497336 D.W.Abbott, M.A.Higgins, S.Hyrnuik, B.Pluvinage, A.Lammerts van Bueren, and A.B.Boraston (2010).
The molecular basis of glycogen breakdown and transport in Streptococcus pneumoniae.
  Mol Microbiol, 77, 183-199.
PDB codes: 2xd2 2xd3
20522493 M.L.Ferrando, S.Fuentes, A.de Greeff, H.Smith, and J.M.Wells (2010).
ApuA, a multifunctional alpha-glucan-degrading enzyme of Streptococcus suis, mediates adhesion to porcine epithelium and mucus.
  Microbiology, 156, 2818-2828.  
20331791 S.J.King (2010).
Pneumococcal modification of host sugars: a major contributor to colonization of the human airway?
  Mol Oral Microbiol, 25, 15-24.  
  20571573 T.J.Boltje, J.H.Kim, J.Park, and G.J.Boons (2010).
Chiral-auxiliary-mediated 1,2-cis-glycosylations for the solid-supported synthesis of a biologically important branched alpha-glucan.
  Nat Chem, 2, 552-557.  
19721085 A.H.Nobbs, R.J.Lamont, and H.F.Jenkinson (2009).
Streptococcus adherence and colonization.
  Microbiol Mol Biol Rev, 73, 407.  
19218457 C.Montanier, A.L.van Bueren, C.Dumon, J.E.Flint, M.A.Correia, J.A.Prates, S.J.Firbank, R.J.Lewis, G.G.Grondin, M.G.Ghinet, T.M.Gloster, C.Herve, J.P.Knox, B.G.Talbot, J.P.Turkenburg, J.Kerovuo, R.Brzezinski, C.M.Fontes, G.J.Davies, A.B.Boraston, and H.J.Gilbert (2009).
Evidence that family 35 carbohydrate binding modules display conserved specificity but divergent function.
  Proc Natl Acad Sci U S A, 106, 3065-3070.
PDB codes: 2vzp 2vzq 2vzr 2w1w 2w3j 2w46 2w47 2w87
19422833 E.Ficko-Blean, and A.B.Boraston (2009).
N-acetylglucosamine recognition by a family 32 carbohydrate-binding module from Clostridium perfringens NagH.
  J Mol Biol, 390, 208-220.
PDB codes: 2w1q 2w1s 2w1u 2wdb
19270088 J.K.Jeong, O.Kwon, Y.M.Lee, D.B.Oh, J.M.Lee, S.Kim, E.H.Kim, T.N.Le, D.K.Rhee, and H.A.Kang (2009).
Characterization of the Streptococcus pneumoniae BgaC protein as a novel surface beta-galactosidase with specific hydrolysis activity for the Galbeta1-3GlcNAc moiety of oligosaccharides.
  J Bacteriol, 191, 3011-3023.  
19382205 J.P.Turkenburg, A.M.Brzozowski, A.Svendsen, T.V.Borchert, G.J.Davies, and K.S.Wilson (2009).
Structure of a pullulanase from Bacillus acidopullulyticus.
  Proteins, 76, 516-519.
PDB code: 2wan
19329633 L.J.Gourlay, I.Santi, A.Pezzicoli, G.Grandi, M.Soriani, and M.Bolognesi (2009).
Group B streptococcus pullulanase crystal structures in the context of a novel strategy for vaccine development.
  J Bacteriol, 191, 3544-3552.
PDB codes: 3faw 3fax
19285508 M.A.Higgins, D.W.Abbott, M.J.Boulanger, and A.B.Boraston (2009).
Blood group antigen recognition by a solute-binding protein from a serotype 3 strain of Streptococcus pneumoniae.
  J Mol Biol, 388, 299-309.
PDB code: 2w7y
19608744 M.A.Higgins, G.E.Whitworth, N.El Warry, M.Randriantsoa, E.Samain, R.D.Burke, D.J.Vocadlo, and A.B.Boraston (2009).
Differential recognition and hydrolysis of host carbohydrate antigens by Streptococcus pneumoniae family 98 glycoside hydrolases.
  J Biol Chem, 284, 26161-26173.
PDB codes: 2wmf 2wmg 2wmh 2wmi 2wmj 2wmk
19735442 S.A.Shelburne, D.B.Keith, M.T.Davenport, S.B.Beres, R.K.Carroll, and J.M.Musser (2009).
Contribution of AmyA, an extracellular alpha-glucan degrading enzyme, to group A streptococcal host-pathogen interaction.
  Mol Microbiol, 74, 159-174.  
19023424 I.Santi, A.Pezzicoli, M.Bosello, F.Berti, M.Mariani, J.L.Telford, G.Grandi, and M.Soriani (2008).
Functional characterization of a newly identified group B streptococcus pullulanase eliciting antibodies able to prevent alpha-glucans degradation.
  PLoS ONE, 3, e3787.  
18366340 J.A.Preston, and D.H.Dockrell (2008).
Virulence factors in pneumococcal respiratory pathogenesis.
  Future Microbiol, 3, 205-221.  
18347045 J.H.Carlson, W.M.Whitmire, D.D.Crane, L.Wicke, K.Virtaneva, D.E.Sturdevant, J.J.Kupko, S.F.Porcella, N.Martinez-Orengo, R.A.Heinzen, L.Kari, and H.D.Caldwell (2008).
The Chlamydia trachomatis plasmid is a transcriptional regulator of chromosomal genes and a virulence factor.
  Infect Immun, 76, 2273-2283.  
18292090 K.J.Gregg, R.Finn, D.W.Abbott, and A.B.Boraston (2008).
Divergent modes of glycan recognition by a new family of carbohydrate-binding modules.
  J Biol Chem, 283, 12604-12613.
PDB codes: 2vmg 2vmh 2vmi 2vng 2vno 2vnr
18508271 S.A.Shelburne, M.T.Davenport, D.B.Keith, and J.M.Musser (2008).
The role of complex carbohydrate catabolism in the pathogenesis of invasive streptococci.
  Trends Microbiol, 16, 318-325.  
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.