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Reitz AB , Ramirez UD , Stith L , Du Y , Smith GR , Jaffe EK
Pseudomonas aeruginosa porphobilinogen synthase assembly state regulators: hit discovery and initial SAR studies
ARKIVOC. 2010 Jun;2010 :175-188
PMID: 21643541 PMCID: PMC3106444 URL: https://www.ncbi.nlm.nih.gov/pubmed/21643541
AbstractPorphobilinogen synthase (PBGS) catalyzes the first common step in the biosynthesis of the essential heme, chlorophyll and vitamin B(12) heme pigments. PBGS activity is regulated by assembly state, with certain oligomers exhibiting biological activity and others either partially or completely inactive, affording an innovative means of allosteric drug action. Pseudomonas aeruginosa PBGS is functionally active as an octamer, and inactive as a dimer. We have identified a series of compounds that stabilize the inactive P. aeruginosa dimer by a computational prescreen followed by native PAGE gel mobility shift analysis. From those results, we have prepared related thiadiazoles and evaluated their ability to regulate P. aeruginosa PBGS assembly state.
NotesReitz, Allen B Ramirez, Ursula D Stith, Linda Du, Yanming Smith, Garry R Jaffe, Eileen K eng R21 AI063324/AI/NIAID NIH HHS/ R43 AI084224-02/AI/NIAID NIH HHS/ T32 CA009035-34/CA/NCI NIH HHS/ R43 AI084224/AI/NIAID NIH HHS/ R21 AI063324-01/AI/NIAID NIH HHS/ R21 AI063324-02/AI/NIAID NIH HHS/ R43 AI084224-01/AI/NIAID NIH HHS/ T32 CA009035/CA/NCI NIH HHS/ P30 CA006927/CA/NCI NIH HHS/ P30 CA006927-41/CA/NCI NIH HHS/ Switzerland ARKIVOC. 2010 Jun;2010:175-188.