PDBsum entry 4l0l

Penicillin binding protein/antibiotic

PDB id: 4l0l

Contents

Protein chain

501 a.a.

Ligands

PFV

Waters ×256

PDB id:

4l0l

Name:

Penicillin binding protein/antibiotic

Title:

Crystal structure of p.Aeruginosa pbp3 in complex with compound 4

Structure:

Penicillin-binding protein 3. Chain: a. Engineered: yes

Source:

Pseudomonas aeruginosa. Organism_taxid: 287. Gene: pbpb. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.10Å R-factor: 0.211 R-free: 0.275

Authors:

S.Han,E.S.Marr

Key ref:

M.F.Brown et al. (2013). Pyridone-conjugated monobactam antibiotics with gram-negative activity. J Med Chem, 56, 5541-5552. PubMed id: 23755848 DOI: 10.1021/jm400560z

Date:

31-May-13 Release date: 21-Aug-13

Protein chain

Q51504  (Q51504_PSEAI) -  Peptidoglycan D,D-transpeptidase FtsI from Pseudomonas aeruginosa

Seq: 579 a.a.

Struc: 501 a.a.

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

DOI no: 10.1021/jm400560z

J Med Chem 56:5541-5552 (2013)

PubMed id: 23755848

Pyridone-conjugated monobactam antibiotics with gram-negative activity.

M.F.Brown, M.J.Mitton-Fry, J.T.Arcari, R.Barham, J.Casavant, B.S.Gerstenberger, S.Han, J.R.Hardink, T.M.Harris, T.Hoang, M.D.Huband, M.S.Lall, M.M.Lemmon, C.Li, J.Lin, S.P.McCurdy, E.McElroy, C.McPherson, E.S.Marr, J.P.Mueller, L.Mullins, A.A.Nikitenko, M.C.Noe, J.Penzien, M.S.Plummer, B.P.Schuff, V.Shanmugasundaram, J.T.Starr, J.Sun, A.Tomaras, J.A.Young, R.P.Zaniewski.

ABSTRACT

Herein we describe the structure-aided design and synthesis of a series of pyridone-conjugated monobactam analogues with in vitro antibacterial activity against clinically relevant Gram-negative species including Pseudomonas aeruginosa , Klebsiella pneumoniae , and Escherichia coli . Rat pharmacokinetic studies with compound 17 demonstrate low clearance and low plasma protein binding. In addition, evidence is provided for a number of analogues suggesting that the siderophore receptors PiuA and PirA play a role in drug uptake in P. aeruginosa strain PAO1.