PDBsum entry: 2bg1

Peptidoglycan

PDB-id

2bg1

Contents

Description

Header details

Protein chain

Ligands

SO4

Metal ions

_CL

Waters ×386

* Residue conservation analysis

Tools

Image Generation

AstexViewer™@PDBe

Run PROCHECK

Clefts Calculation

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.

UniProt:

O70038 (O70038_STRPN)

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

821 a.a.

Struc:

456 a.a.*

Key:		PfamA domain			PfamB domain
		Secondary structure

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

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

Quick_links

RCSB

PDBe

SRS

MMDB

JenaLib

OCA

Proteopedia

CATH

SCOP

FSSP

HSSP

PDBSWS

PQS

CSA

ProSAT

Whatcheck

EDS

Procheck

Clefts

Surface

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

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.

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.

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.

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.

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.