PDBsum entry 3a3f

Hydrolase

PDB id: 3a3f

Contents

Protein chains

453 a.a. *

Ligands

FMZ ×2

Waters ×288

* Residue conservation analysis

PDB id:

3a3f

Name:

Hydrolase

Title:

Crystal structure of penicillin binding protein 4 (dacb) from haemophilus influenzae,complexed with novel beta-lactam (fmz)

Structure:

Penicillin-binding protein 4. Chain: a, b. Fragment: unp residues 28-479. Synonym: pbp4. Engineered: yes

Source:

Haemophilus influenzae. Organism_taxid: 727. Gene: dacb. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.10Å R-factor: 0.192 R-free: 0.236

Authors:

F.Kawai,D.I.Roper,S.-Y.Park,J.R.H.Tame

Key ref:

F.Kawai et al. (2010). Crystal structures of penicillin-binding proteins 4 and 5 from Haemophilus influenzae. J Mol Biol, 396, 634-645. PubMed id: 19958776

Date:

12-Jun-09 Release date: 22-Dec-09

Protein chains

A8E0K8  (A8E0K8_HAEIF) -  Penicillin-binding protein 4 from Haemophilus influenzae

Seq: 479 a.a.

Struc: 453 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.16.4 - serine-type D-Ala-D-Ala carboxypeptidase.
• Reaction: D-alanyl-D-alanine + H₂O = 2 D-alanine

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

J Mol Biol 396:634-645 (2010)

PubMed id: 19958776

Crystal structures of penicillin-binding proteins 4 and 5 from Haemophilus influenzae.

F.Kawai, T.B.Clarke, D.I.Roper, G.J.Han, K.Y.Hwang, S.Unzai, E.Obayashi, S.Y.Park, J.R.Tame.

ABSTRACT

We have determined high-resolution apo crystal structures of two low molecular weight penicillin-binding proteins (PBPs), PBP4 and PBP5, from Haemophilus influenzae, one of the most frequently found pathogens in the upper respiratory tract of children. Novel beta-lactams with notable antimicrobial activity have been designed, and crystal structures of PBP4 complexed with ampicillin and two of the novel molecules have also been determined. Comparing the apo form with those of the complexes, we find that the drugs disturb the PBP4 structure and weaken X-ray diffraction, to very different extents. PBP4 has recently been shown to act as a sensor of the presence of penicillins in Pseudomonas aeruginosa, and our models offer a clue to the structural basis for this effect. Covalently attached penicillins press against a phenylalanine residue near the active site and disturb the deacylation step. The ready inhibition of PBP4 by beta-lactams compared to PBP5 also appears to be related to the weaker interactions holding key residues in a catalytically competent position.