4L0L

Crystal structure of P.aeruginosa PBP3 in complex with compound 4

Summary for 4L0L

• Entry DOI: 10.2210/pdb4l0l/pdb
• Descriptor: Penicillin-binding protein 3, (6R,7S,10Z)-10-(2-amino-1,3-thiazol-4-yl)-1-(1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-yl)-7-formyl-13,13-dimethyl-3,9-dioxo-6-(sulfoamino)-12-oxa-2,4,8,11-tetraazatetradec-10-en-14-oic acid (3 entities in total)
• Functional Keywords: penicillin binding protein 3, penicillin binding protein-antibiotic complex, penicillin binding protein/antibiotic
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 58825.91

Authors

Han, S.,Marr, E.S. (deposition date: 2013-05-31, release date: 2013-08-21, Last modification date: 2024-10-09)

Primary citation

Brown, M.F.,Mitton-Fry, M.J.,Arcari, J.T.,Barham, R.,Casavant, J.,Gerstenberger, B.S.,Han, S.,Hardink, J.R.,Harris, T.M.,Hoang, T.,Huband, M.D.,Lall, M.S.,Lemmon, M.M.,Li, C.,Lin, J.,McCurdy, S.P.,McElroy, E.,McPherson, C.,Marr, E.S.,Mueller, J.P.,Mullins, L.,Nikitenko, A.A.,Noe, M.C.,Penzien, J.,Plummer, M.S.,Schuff, B.P.,Shanmugasundaram, V.,Starr, J.T.,Sun, J.,Tomaras, A.,Young, J.A.,Zaniewski, R.P.
Pyridone-conjugated monobactam antibiotics with gram-negative activity.
J.Med.Chem., 56:5541-5552, 2013

PubMed 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.

PubMed: 23755848
DOI: 10.1021/jm400560z

Experimental method

X-RAY DIFFRACTION (2.1 Å)