PDBsum entry 2bml

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Choline-binding domain PDB id
Protein chains
125 a.a. *
TRS ×2
P6G ×2
SO4 ×3
Waters ×55
* Residue conservation analysis
PDB id:
Name: Choline-binding domain
Title: Ofloxacin-like antibiotics inhibit pneumococcal cell wall degrading virulence factors
Structure: Autolysin. Chain: a, b. Fragment: choline-binding domain, residues 193-318. Synonym: n-acetylmuramoyl-l-alanine amidase, murein, hydrolase, mucopeptide aminohydrolase, cell wall hydrolase. Engineered: yes
Source: Streptococcus pneumoniae. Organism_taxid: 1313. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
2.6Å     R-factor:   0.220     R-free:   0.280
Authors: C.Fernandez-Tornero,G.Gimenez-Gallego,A.Romero,E.Garcia, B.D.Pascual-Teresa,R.Lopez
Key ref:
C.Fernández-Tornero et al. (2005). Ofloxacin-like antibiotics inhibit pneumococcal cell wall-degrading virulence factors. J Biol Chem, 280, 19948-19957. PubMed id: 15769740 DOI: 10.1074/jbc.M501236200
15-Mar-05     Release date:   30-Mar-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P06653  (ALYS_STRPN) -  Autolysin
318 a.a.
125 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.  - 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: 10.1074/jbc.M501236200 J Biol Chem 280:19948-19957 (2005)
PubMed id: 15769740  
Ofloxacin-like antibiotics inhibit pneumococcal cell wall-degrading virulence factors.
C.Fernández-Tornero, E.García, Pascual-Teresa, R.López, G.Giménez-Gallego, A.Romero.
The search for new drugs against Streptococcus pneumoniae (pneumococcus) is driven by the 1.5 million deaths it causes annually. Choline-binding proteins attach to the pneumococcal cell wall through domains that recognize choline moieties, and their involvement in pneumococcal virulence makes them potential targets for drug development. We have defined chemical criteria involved in the docking of small molecules from a three-dimensional structural library to the major pneumococcal autolysin (LytA) choline binding domain. These criteria were used to identify compounds that could interfere with the attachment of this protein to the cell wall, and several quinolones that fit this framework were found to inhibit the cell wall-degrading activity of LytA. Furthermore, these compounds produced similar effects on other enzymes with different catalytic activities but that contained a similar choline binding domain; that is, autolysin (LytC) and the phage lytic enzyme (Cpl-1). Finally, we resolved the crystal structure of the complex between the choline binding domain of LytA and ofloxacin at a resolution of 2.6 Angstroms. These data constitute an important launch pad from which effective drugs to combat pneumococcal infections can be developed.
  Selected figure(s)  
Figure 3.
FIG. 3. Crystal structure of dextrofloxacin bound to a ChBS of C-LytA. A, stereo view of the 2 F[o] - F[c] map of dextrofloxacin in the ChBS of C-LytA, contoured at 1 . Density is well defined for the dextrofloxacin molecule. All the molecules have been represented as ball and stick. Yellow, red, blue, and green have been used to color C, O, N, and F atoms, respectively. B, a solid surface representation of the ChBS with bound dextrofloxacin. The hydrophobic residues and the dextrofloxacin molecule are represented as ball and stick, with C, O, N, and F atoms colored yellow, red, blue, and magenta, respectively. The electrostatic surface potential contoured from -15 (intense red) to +15 kiloteslas (intense blue). The figure was generated with GRASP (45).
Figure 4.
FIG. 4. Geometry of dextrofloxacin at the ChBS in C-LytA. A, diagram of the interactions of dextrofloxacin with C-LytA. Carbon atoms are colored black, oxygens are red, and nitrogens are blue. Hydrogen bonds are symbolized by broken lines. Spiked atoms correspond to those involved in hydrophobic contacts, and spiked circle segments surround hydrophobic van der Waals partners. This figure was drawn with LIGPLOT (7). B, stereo view of the superimposition of the dextrofloxacin molecule at the ChBS as observed in the crystal structure (yellow) and modeled with AutoDock (cyan).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 19948-19957) copyright 2005.  
  Figures were selected by the author.  

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.  
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.  
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
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