5KH4

Crystal Structure of Steptococcus pneumoniae Undecaprenyl pyrophosphate Synthase (UPPS) with FARNESYL DIPHOSPHATE

Summary for 5KH4

• Entry DOI: 10.2210/pdb5kh4/pdb
• Descriptor: Isoprenyl transferase, FARNESYL DIPHOSPHATE (2 entities in total)
• Functional Keywords: upps, native, bacterial, undecaprenyl s. pneumoniae, transferase
• Biological source: Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
• Total number of polymer chains: 2
• Total formula weight: 62587.06

Authors

Concha, N.O. (deposition date: 2016-06-14, release date: 2016-07-20, Last modification date: 2024-03-06)

Primary citation

Concha, N.,Huang, J.,Bai, X.,Benowitz, A.,Brady, P.,Grady, L.C.,Kryn, L.H.,Holmes, D.,Ingraham, K.,Jin, Q.,Pothier Kaushansky, L.,McCloskey, L.,Messer, J.A.,O'Keefe, H.,Patel, A.,Satz, A.L.,Sinnamon, R.H.,Schneck, J.,Skinner, S.R.,Summerfield, J.,Taylor, A.,Taylor, J.D.,Evindar, G.,Stavenger, R.A.
Discovery and Characterization of a Class of Pyrazole Inhibitors of Bacterial Undecaprenyl Pyrophosphate Synthase.
J.Med.Chem., 59:7299-7304, 2016

PubMed Abstract: Undecaprenyl pyrophosphate synthase (UppS) is an essential enzyme in bacterial cell wall synthesis. Here we report the discovery of Staphylococcus aureus UppS inhibitors from an Encoded Library Technology screen and demonstrate binding to the hydrophobic substrate site through cocrystallography studies. The use of bacterial strains with regulated uppS expression and inhibitor resistant mutant studies confirmed that the whole cell activity was the result of UppS inhibition, validating UppS as a druggable antibacterial target.

PubMed: 27379833
DOI: 10.1021/acs.jmedchem.6b00746

Experimental method

X-RAY DIFFRACTION (3.2 Å)