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PDBsum entry 1gvm

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protein ligands Protein-protein interface(s) links
Choline-binding domain PDB id
1gvm
Jmol
Contents
Protein chains
127 a.a. *
134 a.a. *
Ligands
CHT ×20
DDQ
TRS
Waters ×79
* Residue conservation analysis
PDB id:
1gvm
Name: Choline-binding domain
Title: Choline binding domain of the major autolysin (c-lyta) from streptococcus pneumoniae
Structure: Autolysin. Chain: a, b, c, d, e, f. Synonym: major autolysin, n-acetylmuramoyl-l-alanine amidase, murein hydrolase, mucopeptide aminohydrolase, cell wall hydrolase. Engineered: yes
Source: Streptococcus pneumoniae. Pneumococcus. Organism_taxid: 1313. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
Resolution:
2.8Å     R-factor:   0.226     R-free:   0.294
Authors: C.Fernandez-Tornero,R.Lopez,E.Garcia,G.Gimenez-Gallego, A.Romero
Key ref:
C.Fernández-Tornero et al. (2002). Two new crystal forms of the choline-binding domain of the major pneumococcal autolysin: insights into the dynamics of the active homodimer. J Mol Biol, 321, 163-173. PubMed id: 12139941 DOI: 10.1016/S0022-2836(02)00596-X
Date:
15-Feb-02     Release date:   01-Aug-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P06653  (ALYS_STRPN) -  Autolysin
Seq:
Struc:
318 a.a.
127 a.a.*
Protein chain
Pfam   ArchSchema ?
P06653  (ALYS_STRPN) -  Autolysin
Seq:
Struc:
318 a.a.
134 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F: 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: 10.1016/S0022-2836(02)00596-X J Mol Biol 321:163-173 (2002)
PubMed id: 12139941  
 
 
Two new crystal forms of the choline-binding domain of the major pneumococcal autolysin: insights into the dynamics of the active homodimer.
C.Fernández-Tornero, E.García, R.López, G.Giménez-Gallego, A.Romero.
 
  ABSTRACT  
 
Very little is known about the in vivo regulation of the catalytic activity of the major pneumococcal autolysin (LytA), a surface-exposed enzyme that rules the self-destruction of pneumococcal cells through degradation of their peptidoglycan backbone. Two new crystal forms of the cell wall anchoring domain of LytA were obtained, and their structures were solved and refined to 2.4A and 2.8A resolution. The domain is a homodimer with a boomerang-like shape in which the tertiary structure of each monomer is comprised by six independent beta hairpins arranged in a superhelical fashion. Choline molecules at the hydrophobic interface of consecutive hairpins maintain this unique structure. The C-terminal hairpin (last 13 residues of LytA) in the solenoid is responsible for the formation of the catalytically active homodimer. Although the general fold in the structures derived from both crystal forms is essentially the same, two different conformations of the basic homodimer are observed. Biochemical approaches have demonstrated the fundamental role of the 11 C-terminal residues in the catalytic activity of LytA. The studies reported here reveal the importance of some amino acid residues at the C terminus in the determination of the relative distance of the active dimeric form of the autolysin, which appears to be essential for the catalytic activity of this enzyme.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Overall fold of LytA ChBD. (a) Stereo ribbon diagram of the dimeric ChBD of LytA with b strand assignment. Monomers A and B are differently colored (yellow and cyan). A broken line has been drawn to point out the 2-fold non-crystallographic symmetry axis relating the monomers. (b) Ribbon diagram of the dimerization interface, using the same color scheme as in (a). The hairpins, and their constituent strands, responsible for dimerization are labeled. The different torsion of hairpin 6 (hp6) makes the dimerization possible by turning it perpendicular to hairpin 5 (hp5). (c) Stereo view of the hydrophobic and H-bond interaction between monomers A and B at the dimerization interface, in the same orientation as in (b). The side-chains of the most important residues are represented in the ball-and-stick format, the sticks in the color of the corresponding monomer. The H-bonds are drawn as broken green lines. Only residues from one monomer are labeled for simplicity, as the name of the corresponding ones in the other monomer may be inferred. The Figure was prepared using MOLSCRIPT[39] and Raster3D. [40]
Figure 4.
Figure 4. Choline-binding sites. (a) Molecular surface representation of the ChBD dimeric structure derived from the monoclinic crystals, with bound choline molecules drawn as green spheres occupying small hydrophobic cavities. The protein surface is mostly non-charged and locally acidic (red) or basic (blue). (b) Choline-binding sites 1 and 2 in one of the monomers of the monoclinic crystal form. The side-chains of the conserved residues forming the cavity are shown in the ball-and-stick format. Choline molecules at these sites are colored gray.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 321, 163-173) copyright 2002.  
  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.  
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.  
17554049 H.Bierne, and P.Cossart (2007).
Listeria monocytogenes surface proteins: from genome predictions to function.
  Microbiol Mol Biol Rev, 71, 377-397.  
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.  
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
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
15968042 L.Kausmally, O.Johnsborg, M.Lunde, E.Knutsen, and L.S.Håvarstein (2005).
Choline-binding protein D (CbpD) in Streptococcus pneumoniae is essential for competence-induced cell lysis.
  J Bacteriol, 187, 4338-4345.  
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.  
14960577 C.Yuan, and C.Kent (2004).
Identification of critical residues of choline kinase A2 from Caenorhabditis elegans.
  J Biol Chem, 279, 17801-17809.  
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.  
12464609 A.Haro, M.Vélez, E.Goormaghtigh, S.Lago, J.Vázquez, D.Andreu, and M.Gasset (2003).
Reconstitution of holin activity with a synthetic peptide containing the 1-32 sequence region of EJh, the EJ-1 phage holin.
  J Biol Chem, 278, 3929-3936.  
12620121 V.Anantharaman, and L.Aravind (2003).
Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes.
  Genome Biol, 4, R11.  
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 code is shown on the right.