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PDBsum entry 2uwx

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protein ligands metals links
Transferase PDB id
2uwx
Jmol
Contents
Protein chain
469 a.a. *
Ligands
SO4
EDO
Metals
_CL ×2
Waters ×322
* Residue conservation analysis
PDB id:
2uwx
Name: Transferase
Title: Active site restructuring regulates ligand recognition in class a penicillin-binding proteins
Structure: Penicillin-binding protein 1b. Chain: a. Fragment: residues 101-125,323-791. Engineered: yes. Mutation: yes
Source: Streptococcus pneumoniae. Organism_taxid: 171101. Strain: r6. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
2.39Å     R-factor:   0.168     R-free:   0.218
Authors: P.Macheboeuf,A.M.Diguilmi,V.Job,T.Vernet,O.Dideberg, A.Dessen
Key ref:
P.Macheboeuf et al. (2005). Active site restructuring regulates ligand recognition in class A penicillin-binding proteins. Proc Natl Acad Sci U S A, 102, 577-582. PubMed id: 15637155 DOI: 10.1073/pnas.0407186102
Date:
23-Mar-07     Release date:   03-Apr-07    
Supersedes: 2bg3
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q7CRA4  (Q7CRA4_STRR6) -  Penicillin-binding protein 1b
Seq:
Struc:
 
Seq:
Struc:
821 a.a.
469 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 14 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.4.1.129  - Peptidoglycan glycosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Peptidoglycan Biosynthesis (Part 3)
      Reaction: (GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala))(n)- diphosphoundecaprenol + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys- D-Ala-D-Ala)-diphosphoundecaprenol = (GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala- gamma-D-Glu-L-Lys-D-Ala-D-Ala))(n+1)-diphosphoundecaprenol + undecaprenyl diphosphate
(GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala))(n)- diphosphoundecaprenol
+ GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys- D-Ala-D-Ala)-diphosphoundecaprenol
= (GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala- gamma-D-Glu-L-Lys-D-Ala-D-Ala))(n+1)-diphosphoundecaprenol
+ undecaprenyl diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     penicillin binding     1 term  

 

 
    Key reference    
 
 
DOI no: 10.1073/pnas.0407186102 Proc Natl Acad Sci U S A 102:577-582 (2005)
PubMed id: 15637155  
 
 
Active site restructuring regulates ligand recognition in class A penicillin-binding proteins.
P.Macheboeuf, A.M.Di Guilmi, V.Job, T.Vernet, O.Dideberg, A.Dessen.
 
  ABSTRACT  
 
Bacterial cell division is a complex, multimolecular process that requires biosynthesis of new peptidoglycan by penicillin-binding proteins (PBPs) during cell wall elongation and septum formation steps. Streptococcus pneumoniae has three bifunctional (class A) PBPs that catalyze both polymerization of glycan chains (glycosyltransfer) and cross-linking of pentapeptidic bridges (transpeptidation) during the peptidoglycan biosynthetic process. In addition to playing important roles in cell division, PBPs are also the targets for beta-lactam antibiotics and thus play key roles in drug-resistance mechanisms. The crystal structure of a soluble form of pneumococcal PBP1b (PBP1b*) has been solved to 1.9 A, thus providing previously undescribed structural information regarding a class A PBP from any organism. PBP1b* is a three-domain molecule harboring a short peptide from the glycosyltransferase domain bound to an interdomain linker region, the transpeptidase domain, and a C-terminal region. The structure of PBP1b* complexed with beta-lactam antibiotics reveals that ligand recognition requires a conformational modification involving conserved elements within the cleft. The open and closed structures of PBP1b* suggest how class A PBPs may become activated as novel peptidoglycan synthesis becomes necessary during the cell division process. In addition, this structure provides an initial framework for the understanding of the role of class A PBPs in the development of antibiotic resistance.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Surface representation of PBP1b^*, with the GT/TP interdomain linker region shown as a red C^ . Hydrophobic residues are shown in green.
Figure 5.
Fig. 5. Surface representation of PBP1b^* in closed and open conformations. (A) In the closed conformation, the active site is blocked and unavailable for binding. (B) Opening of the catalytic gorge reveals an elongated binding cleft with the active site (shown in red) at the bottom. A surface-exposed hydrophobic patch could stabilize the GT domain and position it axially with respect to the TP active site.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20974151 S.Sainsbury, L.Bird, V.Rao, S.M.Shepherd, D.I.Stuart, W.N.Hunter, R.J.Owens, and J.Ren (2011).
Crystal structures of penicillin-binding protein 3 from Pseudomonas aeruginosa: comparison of native and antibiotic-bound forms.
  J Mol Biol, 405, 173-184.
PDB codes: 3oc2 3ocl 3ocn
20849416 J.Offant, M.Terrak, A.Derouaux, E.Breukink, M.Nguyen-Distèche, A.Zapun, and T.Vernet (2010).
Optimization of conditions for the glycosyltransferase activity of penicillin-binding protein 1a from Thermotoga maritima.
  FEBS J, 277, 4290-4298.  
18986991 A.J.Powell, J.Tomberg, A.M.Deacon, R.A.Nicholas, and C.Davies (2009).
Crystal structures of penicillin-binding protein 2 from penicillin-susceptible and -resistant strains of Neisseria gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance.
  J Biol Chem, 284, 1202-1212.
PDB codes: 3equ 3eqv
18721881 A.L.Lovering, M.Gretes, and N.C.Strynadka (2008).
Structural details of the glycosyltransferase step of peptidoglycan assembly.
  Curr Opin Struct Biol, 18, 534-543.  
18602645 E.Sauvage, A.J.Powell, J.Heilemann, H.R.Josephine, P.Charlier, C.Davies, and R.F.Pratt (2008).
Crystal structures of complexes of bacterial DD-peptidases with peptidoglycan-mimetic ligands: the substrate specificity puzzle.
  J Mol Biol, 381, 383-393.
PDB codes: 2vgj 2vgk 3beb 3bec
18266856 E.Sauvage, F.Kerff, M.Terrak, J.A.Ayala, and P.Charlier (2008).
The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis.
  FEMS Microbiol Rev, 32, 234-258.  
  18391428 M.Yamada, T.Watanabe, N.Baba, T.Miyara, J.Saito, and Y.Takeuchi (2008).
Crystallization and preliminary crystallographic analysis of the transpeptidase domain of penicillin-binding protein 2B from Streptococcus pneumoniae.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 284-288.  
18391040 M.Yamada, T.Watanabe, N.Baba, Y.Takeuchi, F.Ohsawa, and S.Gomi (2008).
Crystal structures of biapenem and tebipenem complexed with penicillin-binding proteins 2X and 1A from Streptococcus pneumoniae.
  Antimicrob Agents Chemother, 52, 2053-2060.
PDB codes: 2zc3 2zc4 2zc5 2zc6
17374723 E.Santillana, A.Beceiro, G.Bou, and A.Romero (2007).
Crystal structure of the carbapenemase OXA-24 reveals insights into the mechanism of carbapenem hydrolysis.
  Proc Natl Acad Sci U S A, 104, 5354-5359.
PDB code: 2jc7
17724158 M.Yamada, T.Watanabe, T.Miyara, N.Baba, J.Saito, Y.Takeuchi, and F.Ohsawa (2007).
Crystal structure of cefditoren complexed with Streptococcus pneumoniae penicillin-binding protein 2X: structural basis for its high antimicrobial activity.
  Antimicrob Agents Chemother, 51, 3902-3907.
PDB codes: 2z2l 2z2m
17676039 P.Macheboeuf, D.S.Fischer, T.Brown, A.Zervosen, A.Luxen, B.Joris, A.Dessen, and C.J.Schofield (2007).
Structural and mechanistic basis of penicillin-binding protein inhibition by lactivicins.
  Nat Chem Biol, 3, 565-569.
PDB codes: 2jch 2je5
17360321 Y.Yuan, D.Barrett, Y.Zhang, D.Kahne, P.Sliz, and S.Walker (2007).
Crystal structure of a peptidoglycan glycosyltransferase suggests a model for processive glycan chain synthesis.
  Proc Natl Acad Sci U S A, 104, 5348-5353.
PDB code: 2oqo
16751607 A.L.Lovering, L.De Castro, D.Lim, and N.C.Strynadka (2006).
Structural analysis of an "open" form of PBP1B from Streptococcus pneumoniae.
  Protein Sci, 15, 1701-1709.
PDB code: 2fff
16689786 A.P.Bhavsar, and E.D.Brown (2006).
Cell wall assembly in Bacillus subtilis: how spirals and spaces challenge paradigms.
  Mol Microbiol, 60, 1077-1090.  
16635801 J.J.Barker (2006).
Antibacterial drug discovery and structure-based design.
  Drug Discov Today, 11, 391-404.  
16968223 M.I.Crisóstomo, W.Vollmer, A.S.Kharat, S.Inhülsen, F.Gehre, S.Buckenmaier, and A.Tomasz (2006).
Attenuation of penicillin resistance in a peptidoglycan O-acetyl transferase mutant of Streptococcus pneumoniae.
  Mol Microbiol, 61, 1497-1509.  
16911039 P.Macheboeuf, C.Contreras-Martel, V.Job, O.Dideberg, and A.Dessen (2006).
Penicillin binding proteins: key players in bacterial cell cycle and drug resistance processes.
  FEMS Microbiol Rev, 30, 673-691.  
16537437 S.O.Meroueh, K.Z.Bencze, D.Hesek, M.Lee, J.F.Fisher, T.L.Stemmler, and S.Mobashery (2006).
Three-dimensional structure of the bacterial cell wall peptidoglycan.
  Proc Natl Acad Sci U S A, 103, 4404-4409.  
16803586 U.Bertsche, T.Kast, B.Wolf, C.Fraipont, M.E.Aarsman, K.Kannenberg, M.von Rechenberg, M.Nguyen-Distèche, T.den Blaauwen, J.V.Höltje, and W.Vollmer (2006).
Interaction between two murein (peptidoglycan) synthases, PBP3 and PBP1B, in Escherichia coli.
  Mol Microbiol, 61, 675-690.  
16118062 B.Ostash, and S.Walker (2005).
Bacterial transglycosylase inhibitors.
  Curr Opin Chem Biol, 9, 459-466.  
16339737 D.J.Scheffers, and M.G.Pinho (2005).
Bacterial cell wall synthesis: new insights from localization studies.
  Microbiol Mol Biol Rev, 69, 585-607.  
16129657 M.S.Wilke, A.L.Lovering, and N.C.Strynadka (2005).
Beta-lactam antibiotic resistance: a current structural perspective.
  Curr Opin Microbiol, 8, 525-533.  
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.