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3SH0

Crystal Structure of E. coli undecaprenyl pyrophosphate synthase in complex with BPH-1065

Summary for 3SH0
Entry DOI10.2210/pdb3sh0/pdb
Related3SGT 3SGV 3SGX
DescriptorUndecaprenyl pyrophosphate synthase, 2-(dodecyloxy)-6-hydroxybenzoic acid (3 entities in total)
Functional Keywordsalpha/beta, transferase-transferase inhibitor complex, transferase/transferase inhibitor
Biological sourceEscherichia coli
Total number of polymer chains2
Total formula weight57929.57
Authors
Cao, R.,Liu, Y.-L.,Oldfield, E. (deposition date: 2011-06-15, release date: 2012-12-19, Last modification date: 2023-09-13)
Primary citationZhu, W.,Zhang, Y.,Sinko, W.,Hensler, M.E.,Olson, J.,Molohon, K.J.,Lindert, S.,Cao, R.,Li, K.,Wang, K.,Wang, Y.,Liu, Y.L.,Sankovsky, A.,de Oliveira, C.A.,Mitchell, D.A.,Nizet, V.,McCammon, J.A.,Oldfield, E.
Antibacterial drug leads targeting isoprenoid biosynthesis.
Proc.Natl.Acad.Sci.USA, 110:123-128, 2013
Cited by
PubMed Abstract: With the rise in resistance to antibiotics such as methicillin, there is a need for new drugs. We report here the discovery and X-ray crystallographic structures of 10 chemically diverse compounds (benzoic, diketo, and phosphonic acids, as well as a bisamidine and a bisamine) that inhibit bacterial undecaprenyl diphosphate synthase, an essential enzyme involved in cell wall biosynthesis. The inhibitors bind to one or more of the four undecaprenyl diphosphate synthase inhibitor binding sites identified previously, with the most active leads binding to site 4, outside the catalytic center. The most potent leads are active against Staphylococcus aureus [minimal inhibitory concentration (MIC)(90) ∼0.25 µg/mL], and one potently synergizes with methicillin (fractional inhibitory concentration index = 0.25) and is protective in a mouse infection model. These results provide numerous leads for antibacterial development and open up the possibility of restoring sensitivity to drugs such as methicillin, using combination therapies.
PubMed: 23248302
DOI: 10.1073/pnas.1219899110
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.84 Å)
Structure validation

239149

数据于2025-07-23公开中

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