4WEL

Crystal structure of Pseudomonas aeruginosa PBP3 with SMC-3176

Summary for 4WEL

• Entry DOI: 10.2210/pdb4wel/pdb
• Related: 4WEJ 4WEK
• Descriptor: Penicillin-binding protein 3, (3S,4S,7Z)-7-(2-amino-1,3-thiazol-4-yl)-4-formyl-1-[({3-(5-hydroxy-4-oxo-3,4-dihydropyridin-2-yl)-4-[3-(methylsulfonyl)propyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}sulfonyl)amino]-3,10,10-trimethyl-1,6-dioxo-9-oxa-2,5,8-triazaundec-7-en-11-oic acid (3 entities in total)
• Functional Keywords: inhibitor, siderophore-conjugated monocarbams, pseudomonas aeruginosa, penicillin-binding protein 3, penicillin-binding protein-inhibitor complex, penicillin-binding protein/inhibitor
• Biological source: Pseudomonas aeruginosa PA14
• Total number of polymer chains: 1
• Total formula weight: 59106.23

Authors

Ferguson, A.D. (deposition date: 2014-09-10, release date: 2015-04-22, Last modification date: 2024-11-13)

Primary citation

Murphy-Benenato, K.E.,Dangel, B.,Davis, H.E.,Durand-Reville, T.F.,Ferguson, A.D.,Gao, N.,Jahic, H.,Mueller, J.P.,Manyak, E.L.,Quiroga, O.,Rooney, M.,Sha, L.,Sylvester, M.,Wu, F.,Zambrowski, M.,Zhao, S.X.
SAR and Structural Analysis of Siderophore-Conjugated Monocarbam Inhibitors of Pseudomonas aeruginosa PBP3.
Acs Med.Chem.Lett., 6:537-542, 2015

PubMed Abstract: A main challenge in the development of new agents for the treatment of Pseudomonas aeruginosa infections is the identification of chemotypes that efficiently penetrate the cell envelope and are not susceptible to established resistance mechanisms. Siderophore-conjugated monocarbams are attractive because of their ability to hijack the bacteria's iron uptake machinery for transport into the periplasm and their inherent stability to metallo-β-lactamases. Through development of the SAR we identified a number of modifications to the scaffold that afforded active anti-P. aeruginosa agents with good physicochemical properties. Through crystallographic efforts we gained a better understanding into how these compounds bind to the target penicillin binding protein PBP3 and factors to consider for future design.

PubMed: 26005529
DOI: 10.1021/acsmedchemlett.5b00026

Experimental method

X-RAY DIFFRACTION (1.99 Å)