PDBsum entry 3a3d

Hydrolase

PDB id: 3a3d

Contents

Protein chains

453 a.a. *

Ligands

GOL ×4

Waters ×924

* Residue conservation analysis

PDB id:

3a3d

Name:

Hydrolase

Title:

Crystal structure of penicillin binding protein 4 (dacb) from haemophilus influenzae

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:

1.60Å R-factor: 0.173 R-free: 0.204

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

P45161  (DACB_HAEIN) -  D-alanyl-D-alanine carboxypeptidase DacB from Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)

Seq: 479 a.a.

Struc: 453 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.3.4.16.4 - serine-type D-Ala-D-Ala carboxypeptidase.
• Reaction: D-alanyl-D-alanine + H₂O = 2 D-alanine

+ = 2 × (Bound ligand (Het Group name = GOL) matches with 50.00% similarity)

• Enzyme class 2: E.C.3.4.21.- - ?????

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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.