PDBsum entry: 2bg1

Peptidoglycan

PDB id: 2bg1

Contents

Protein chain

456 a.a. *

Ligands

SO4

Metals

_CL

Waters ×386

* Residue conservation analysis

PDB id:

2bg1

Name:

Peptidoglycan

Title:

Active site restructuring regulates ligand recognition in classa penicillin-binding proteins (pbps)

Structure:

Penicillin-binding protein 1b. Chain: a. Fragment: transpeptidase domain, residues 101-125 and residues 323-791. Synonym: pbp1b. Engineered: yes. Mutation: yes

Source:

Streptococcus pneumoniae. Organism_taxid: 171101. Strain: r6. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.9Å R-factor: 0.201 R-free: 0.226

Authors:

P.Macheboeuf,A.M.Di Guilmi,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:

16-Dec-04 Release date: 11-Mar-05

Protein chain

O70038  (O70038_STRPN) -  Penicillin-binding protein 1B

Seq: 821 a.a.

Struc: 456 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Biological process: peptidoglycan-based cell wall biogenesis (1 term)
• Biochemical function: penicillin binding (1 term)

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.