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PDBsum entry 1h8g

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Choline-binding domain PDB id
1h8g
Jmol
Contents
Protein chains
95 a.a. *
Ligands
CHT ×6
Waters ×61
* Residue conservation analysis
PDB id:
1h8g
Name: Choline-binding domain
Title: C-terminal domain of the major autolysin (c-lyta) from streptococcus pneumoniae
Structure: Major autolysin. Chain: a, b. Fragment: choline-binding domain. Synonym: c-lyta, cell wall binding domain. Engineered: yes
Source: Streptococcus pneumoniae. Organism_taxid: 1313. Cellular_location: extracellular. Gene: lyta. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Biol. unit: Homo-Dimer (from PDB file)
Resolution:
2.4Å     R-factor:   0.219     R-free:   0.263
Authors: C.Fernandez-Tornero,E.Garcia,R.Lopez,G.Gimenez-Gallego, A.Romero
Key ref:
C.Fernández-Tornero et al. (2001). A novel solenoid fold in the cell wall anchoring domain of the pneumococcal virulence factor LytA. Nat Struct Biol, 8, 1020-1024. PubMed id: 11694890 DOI: 10.1038/nsb724
Date:
06-Feb-01     Release date:   31-Jan-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P06653  (ALYS_STRPN) -  Autolysin
Seq:
Struc:
318 a.a.
95 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.5.1.28  - N-acetylmuramoyl-L-alanine amidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolyzes the link between N-acetylmuramoyl residues and L-amino acid residues in certain bacterial cell-wall glycopeptides.

 

 
DOI no: 10.1038/nsb724 Nat Struct Biol 8:1020-1024 (2001)
PubMed id: 11694890  
 
 
A novel solenoid fold in the cell wall anchoring domain of the pneumococcal virulence factor LytA.
C.Fernández-Tornero, R.López, E.García, G.Giménez-Gallego, A.Romero.
 
  ABSTRACT  
 
Choline binding proteins are virulence determinants present in several Gram-positive bacteria. Because anchorage of these proteins to the cell wall through their choline binding domain is essential for bacterial virulence, their release from the cell surface is considered a powerful target for a weapon against these pathogens. The first crystal structure of a choline binding domain, from the toxin-releasing enzyme pneumococcal major autolysin (LytA), reveals a novel solenoid fold consisting exclusively of beta-hairpins that stack to form a left-handed superhelix. This unique structure is maintained by choline molecules at the hydrophobic interface of consecutive hairpins and may be present in other choline binding proteins that share high homology to the repeated motif of the domain.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. The crystal structure of LytA ChBD. a, Stereo ribbon diagram of LytA ChBD with hairpins assignment. Hairpins ('hp') are colored cyan, whereas the loops connecting them are colored yellow. b, Stereo C trace of the C-LytA structure from the front view -- that is, from the N-terminal base of the cylinder. A C trace of a different color is shown for each substructure: red, dark blue, green, orange, light blue and black for hairpins 1 -6, respectively. c, Scheme for the first three steps in a complete turn of the spiral staircase, with the same colors as in (b). The white arrow in the middle indicates the downstairs (N- to C-terminus) direction. This figure was prepared using MOLSCRIPT28.
Figure 3.
Figure 3. Choline binding sites. a, Ribbon diagram of the C-LytA dimer inscribed into the molecular surface. Monomers are highlighted in different colors: yellow and cyan. ChBSs 1 and 2 of monomer 'a' (yellow) are occupied by DDAO molecules. ChBS3 of monomer 'b' (cyan) is occupied by the (2,2':6',2''-terpyridine)-platinum(II) used for MAD phasing. The hydrophobic components of choline (labeled 'cho'), DDAO (labeled 'ddao') and terpyridin (labeled 'tpy') molecules, schematized as CPK, occupy small hydrophobic cavities on the surface of the protein. b, Stereo diagram of ChBS4, where choline is highlighted in orange. The side chains of the hydrophobic conserved residues forming the cavity are shown in the ball-and-stick format. The 2F[o] - F[c] omit map (green) of the choline molecule is contoured at 1.0 .
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 1020-1024) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21051322 B.Maestro, C.M.Santiveri, M.A.Jiménez, and J.M.Sanz (2011).
Structural autonomy of a β-hairpin peptide derived from the pneumococcal choline-binding protein LytA.
  Protein Eng Des Sel, 24, 113-122.  
21229247 R.Fraga Vidal, C.Moulis, P.Escalier, M.Remaud-Siméon, and P.Monsan (2011).
Isolation of a gene from Leuconostoc citreum B/110-1-2 encoding a novel dextransucrase enzyme.
  Curr Microbiol, 62, 1260-1266.  
21118988 A.Vujicic-Zagar, T.Pijning, S.Kralj, C.A.López, W.Eeuwema, L.Dijkhuizen, and B.W.Dijkstra (2010).
Crystal structure of a 117 kDa glucansucrase fragment provides insight into evolution and product specificity of GH70 enzymes.
  Proc Natl Acad Sci U S A, 107, 21406-21411.
PDB codes: 3hz3 3klk 3kll
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.  
19210622 M.Bublitz, L.Polle, C.Holland, D.W.Heinz, M.Nimtz, and W.D.Schubert (2009).
Structural basis for autoinhibition and activation of Auto, a virulence-associated peptidoglycan hydrolase of Listeria monocytogenes.
  Mol Microbiol, 71, 1509-1522.
PDB code: 3fi7
19502408 P.Romero, N.J.Croucher, N.L.Hiller, F.Z.Hu, G.D.Ehrlich, S.D.Bentley, E.García, and T.J.Mitchell (2009).
Comparative genomic analysis of ten Streptococcus pneumoniae temperate bacteriophages.
  J Bacteriol, 191, 4854-4862.  
19217401 Q.Xu, S.Sudek, D.McMullan, M.D.Miller, B.Geierstanger, D.H.Jones, S.S.Krishna, G.Spraggon, B.Bursalay, P.Abdubek, C.Acosta, E.Ambing, T.Astakhova, H.L.Axelrod, D.Carlton, J.Caruthers, H.J.Chiu, T.Clayton, M.C.Deller, L.Duan, Y.Elias, M.A.Elsliger, J.Feuerhelm, S.K.Grzechnik, J.Hale, G.Won Han, J.Haugen, L.Jaroszewski, K.K.Jin, H.E.Klock, M.W.Knuth, P.Kozbial, A.Kumar, D.Marciano, A.T.Morse, E.Nigoghossian, L.Okach, S.Oommachen, J.Paulsen, R.Reyes, C.L.Rife, C.V.Trout, H.van den Bedem, D.Weekes, A.White, G.Wolf, C.Zubieta, K.O.Hodgson, J.Wooley, A.M.Deacon, A.Godzik, S.A.Lesley, and I.A.Wilson (2009).
Structural basis of murein peptide specificity of a gamma-D-glutamyl-l-diamino acid endopeptidase.
  Structure, 17, 303-313.
PDB codes: 2evr 2fg0 2hbw
19633119 S.Campuzano, B.Serra, D.Llull, J.L.García, and P.García (2009).
Cloning, expression, and characterization of a peculiar choline-binding beta-galactosidase from Streptococcus mitis.
  Appl Environ Microbiol, 75, 5972-5980.  
18790485 B.Maestro, I.Velasco, I.Castillejo, M.Arévalo-Rodríguez, A.Cebolla, and J.M.Sanz (2008).
Affinity partitioning of proteins tagged with choline-binding modules in aqueous two-phase systems.
  J Chromatogr A, 1208, 189-196.  
18667432 B.Monterroso, J.L.Sáiz, P.García, J.L.García, and M.Menéndez (2008).
Insights into the Structure-Function Relationships of Pneumococcal Cell Wall Lysozymes, LytC and Cpl-1.
  J Biol Chem, 283, 28618-28628.  
18070889 C.Attali, C.Frolet, C.Durmort, J.Offant, T.Vernet, and A.M.Di Guilmi (2008).
Streptococcus pneumoniae choline-binding protein E interaction with plasminogen/plasmin stimulates migration across the extracellular matrix.
  Infect Immun, 76, 466-476.  
17951381 C.L.Naessan, W.Egge-Jacobsen, R.W.Heiniger, M.C.Wolfgang, F.E.Aas, A.Røhr, H.C.Winther-Larsen, and M.Koomey (2008).
Genetic and functional analyses of PptA, a phospho-form transferase targeting type IV pili in Neisseria gonorrhoeae.
  J Bacteriol, 190, 387-400.  
18371216 M.Zhou, J.Boekhorst, C.Francke, and R.J.Siezen (2008).
LocateP: genome-scale subcellular-location predictor for bacterial proteins.
  BMC Bioinformatics, 9, 173.  
18237396 S.Del Moral, C.Olvera, M.E.Rodriguez, and A.L.Munguia (2008).
Functional role of the additional domains in inulosucrase (IslA) from Leuconostoc citreum CW28.
  BMC Biochem, 9, 6.  
18394902 T.Jank, and K.Aktories (2008).
Structure and mode of action of clostridial glucosylating toxins: the ABCD model.
  Trends Microbiol, 16, 222-229.  
18840883 V.M.Hernández-Rocamora, B.Maestro, A.Mollá-Morales, and J.M.Sanz (2008).
Rational stabilization of the C-LytA affinity tag by protein engineering.
  Protein Eng Des Sel, 21, 709-720.  
18266855 W.Vollmer, B.Joris, P.Charlier, and S.Foster (2008).
Bacterial peptidoglycan (murein) hydrolases.
  FEMS Microbiol Rev, 32, 259-286.  
17229144 B.Maestro, A.González, P.García, and J.M.Sanz (2007).
Inhibition of pneumococcal choline-binding proteins and cell growth by esters of bicyclic amines.
  FEBS J, 274, 364-376.  
17353242 D.Llull, L.Rivas, and E.García (2007).
In vitro bactericidal activity of the antiprotozoal drug miltefosine against Streptococcus pneumoniae and other pathogenic streptococci.
  Antimicrob Agents Chemother, 51, 1844-1848.  
17586649 F.Chi, M.Leider, F.Leendertz, C.Bergmann, C.Boesch, S.Schenk, G.Pauli, H.Ellerbrok, and R.Hakenbeck (2007).
New Streptococcus pneumoniae clones in deceased wild chimpanzees.
  J Bacteriol, 189, 6085-6088.  
17554049 H.Bierne, and P.Cossart (2007).
Listeria monocytogenes surface proteins: from genome predictions to function.
  Microbiol Mol Biol Rev, 71, 377-397.  
17581815 I.Pérez-Dorado, N.E.Campillo, B.Monterroso, D.Hesek, M.Lee, J.A.Páez, P.García, M.Martínez-Ripoll, J.L.García, S.Mobashery, M.Menéndez, and J.A.Hermoso (2007).
Elucidation of the molecular recognition of bacterial cell wall by modular pneumococcal phage endolysin CPL-1.
  J Biol Chem, 282, 24990-24999.
PDB codes: 2ixu 2ixv 2j8f 2j8g
17462028 J.Mitchell, I.R.Siboo, D.Takamatsu, H.F.Chambers, and P.M.Sullam (2007).
Mechanism of cell surface expression of the Streptococcus mitis platelet binding proteins PblA and PblB.
  Mol Microbiol, 64, 844-857.  
17555432 J.P.Claverys, B.Martin, and L.S.Håvarstein (2007).
Competence-induced fratricide in streptococci.
  Mol Microbiol, 64, 1423-1433.  
17439951 P.Romero, R.López, and E.García (2007).
Key role of amino acid residues in the dimerization and catalytic activation of the autolysin LytA, an important virulence factor in Streptococcus pneumoniae.
  J Biol Chem, 282, 17729-17737.  
16428724 B.Mann, C.Orihuela, J.Antikainen, G.Gao, J.Sublett, T.K.Korhonen, and E.Tuomanen (2006).
Multifunctional role of choline binding protein G in pneumococcal pathogenesis.
  Infect Immun, 74, 821-829.  
16487313 M.Desvaux, E.Dumas, I.Chafsey, and M.Hébraud (2006).
Protein cell surface display in Gram-positive bacteria: from single protein to macromolecular protein structure.
  FEMS Microbiol Lett, 256, 1.  
17109095 M.Konno, S.Baba, H.Mikawa, K.Hara, F.Matsumoto, K.Kaga, T.Nishimura, T.Kobayashi, N.Furuya, H.Moriyama, Y.Okamoto, M.Furukawa, N.Yamanaka, T.Matsushima, Y.Yoshizawa, S.Kohno, K.Kobayashi, A.Morikawa, S.Koizumi, K.Sunakawa, M.Inoue, and K.Ubukata (2006).
Study of nasopharyngeal bacterial flora. Second report. Variations in nasopharyngeal bacterial flora in children aged 6 years or younger when administered antimicrobial agents. Part 2.
  J Infect Chemother, 12, 305-330.  
  16820691 N.G.Paterson, A.Riboldi-Tunicliffe, T.J.Mitchell, and N.W.Isaacs (2006).
Overexpression, purification and crystallization of a choline-binding protein CbpI from Streptococcus pneumoniae.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 672-675.  
15769740 C.Fernández-Tornero, E.García, B.de Pascual-Teresa, R.López, G.Giménez-Gallego, and A.Romero (2005).
Ofloxacin-like antibiotics inhibit pneumococcal cell wall-degrading virulence factors.
  J Biol Chem, 280, 19948-19957.
PDB code: 2bml
15601714 E.Fabre, S.Bozonnet, A.Arcache, R.M.Willemot, M.Vignon, P.Monsan, and M.Remaud-Simeon (2005).
Role of the two catalytic domains of DSR-E dextransucrase and their involvement in the formation of highly alpha-1,2 branched dextran.
  J Bacteriol, 187, 296-303.  
15717932 E.Pagliero, O.Dideberg, T.Vernet, and A.M.Di Guilmi (2005).
The PECACE domain: a new family of enzymes with potential peptidoglycan cleavage activity in Gram-positive bacteria.
  BMC Genomics, 6, 19.  
15908436 G.Garau, D.Lemaire, T.Vernet, O.Dideberg, and A.M.Di Guilmi (2005).
Crystal structure of phosphorylcholine esterase domain of the virulence factor choline-binding protein e from streptococcus pneumoniae: new structural features among the metallo-beta-lactamase superfamily.
  J Biol Chem, 280, 28591-28600.
PDB codes: 1wra 2v05
15895092 J.A.Hermoso, L.Lagartera, A.González, M.Stelter, P.García, M.Martínez-Ripoll, J.L.García, and M.Menéndez (2005).
Insights into pneumococcal pathogenesis from the crystal structure of the modular teichoic acid phosphorylcholine esterase Pce.
  Nat Struct Mol Biol, 12, 533-538.
PDB code: 2bib
16344467 J.G.Ho, A.Greco, M.Rupnik, and K.K.Ng (2005).
Crystal structure of receptor-binding C-terminal repeats from Clostridium difficile toxin A.
  Proc Natl Acad Sci U S A, 102, 18373-18378.
PDB code: 2f6e
16332865 M.Moscoso, V.Obregón, R.López, J.L.García, and E.García (2005).
Allelic variation of polymorphic locus lytB, encoding a choline-binding protein, from streptococci of the mitis group.
  Appl Environ Microbiol, 71, 8706-8713.  
15616594 R.Luo, B.Mann, W.S.Lewis, A.Rowe, R.Heath, M.L.Stewart, A.E.Hamburger, S.Sivakolundu, E.R.Lacy, P.J.Bjorkman, E.Tuomanen, and R.W.Kriwacki (2005).
Solution structure of choline binding protein A, the major adhesin of Streptococcus pneumoniae.
  EMBO J, 24, 34-43.
PDB code: 1w9r
15294797 C.Moldes, J.L.García, and P.García (2004).
Construction of a chimeric thermostable pyrophosphatase to facilitate its purification and immobilization by using the choline-binding tag.
  Appl Environ Microbiol, 70, 4642-4647.  
15247237 J.Varea, B.Monterroso, J.L.Sáiz, C.López-Zumel, J.L.García, J.Laynez, P.García, and M.Menéndez (2004).
Structural and thermodynamic characterization of Pal, a phage natural chimeric lysin active against pneumococci.
  J Biol Chem, 279, 43697-43707.  
15576771 P.Romero, R.López, and E.García (2004).
Characterization of LytA-like N-acetylmuramoyl-L-alanine amidases from two new Streptococcus mitis bacteriophages provides insights into the properties of the major pneumococcal autolysin.
  J Bacteriol, 186, 8229-8239.  
15539074 R.López, and E.García (2004).
Recent trends on the molecular biology of pneumococcal capsules, lytic enzymes, and bacteriophage.
  FEMS Microbiol Rev, 28, 553-580.  
14642312 J.Kolberg, A.Aase, G.Rødal, J.E.Littlejohn, and M.J.Jedrzejas (2003).
Epitope mapping of pneumococcal surface protein A of strain Rx1 using monoclonal antibodies and molecular structure modelling.
  FEMS Immunol Med Microbiol, 39, 265-273.  
12151330 A.M.Di Guilmi, and A.Dessen (2002).
New approaches towards the identification of antibiotic and vaccine targets in Streptococcus pneumoniae.
  EMBO Rep, 3, 728-734.  
12193614 B.De Las Rivas, J.L.García, R.López, and P.García (2002).
Purification and polar localization of pneumococcal LytB, a putative endo-beta-N-acetylglucosaminidase: the chain-dispersing murein hydrolase.
  J Bacteriol, 184, 4988-5000.  
12270834 S.Bozonnet, M.Dols-Laffargue, E.Fabre, S.Pizzut, M.Remaud-Simeon, P.Monsan, and R.M.Willemot (2002).
Molecular characterization of DSR-E, an alpha-1,2 linkage-synthesizing dextransucrase with two catalytic domains.
  J Bacteriol, 184, 5753-5761.  
12089276 V.Obregón, P.García, E.García, A.Fenoll, R.López, and J.L.García (2002).
Molecular peculiarities of the lytA gene isolated from clinical pneumococcal strains that are bile insoluble.
  J Clin Microbiol, 40, 2545-2554.  
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.