5YIG

Crystal structure of Streptococcus pneumonia ParE with inhibitor

Summary for 5YIG

• Entry DOI: 10.2210/pdb5yig/pdb
• Descriptor: DNA topoisomerase 4 subunit B, 1-ethyl-3-[5-[2-[(1S,5R)-3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-(2-oxidanylidene-3H-1,3,4-oxadiazol-5-yl)pyridin-3-yl]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-2-yl]urea (3 entities in total)
• Functional Keywords: inhibitor, antimicrobial protein
• Biological source: Streptococcus pneumoniae GA47502
• Total number of polymer chains: 2
• Total formula weight: 46672.53

Authors

Cherian, J.,Tan, Y.,Hill, J. (deposition date: 2017-10-04, release date: 2018-09-05, Last modification date: 2024-03-27)

Primary citation

Ho, S.Y.,Wang, W.,Ng, F.M.,Wong, Y.X.,Poh, Z.Y.,Tan, S.W.E.,Ang, S.H.,Liew, S.S.,Joyner Wong, Y.S.,Tan, Y.,Poulsen, A.,Pendharkar, V.,Sangthongpitag, K.,Manchester, J.,Basarab, G.,Hill, J.,Keller, T.H.,Cherian, J.
Discovery of dual GyrB/ParE inhibitors active against Gram-negative bacteria.
Eur J Med Chem, 157:610-621, 2018

PubMed Abstract: Even though many GyrB and ParE inhibitors have been reported in the literature, few possess activity against Gram-negative bacteria. This is primarily due to limited permeability across Gram-negative bacterial membrane as well as bacterial efflux mechanisms. Permeability of compounds across Gram-negative bacterial membranes depends on many factors including physicochemical properties of the inhibitors. Herein, we show the optimization of pyridylureas leading to compounds with potent activity against Gram-negative bacterial species such as P.aeruginosa, E.coli and A.baumannii.

PubMed: 30125722
DOI: 10.1016/j.ejmech.2018.08.025

Experimental method

X-RAY DIFFRACTION (2.8 Å)