This is an archive of papers published by the staff and faculty of Fox Chase Cancer Center. For questions about content, please contact Talbot Research Library
Last updated on
Reitz AB , Ramirez UD , Stith L , Du YM , Smith GR , Jaffe EK
Pseudomonas aeruginosa porphobilinogen synthase assembly state regulators: hit discovery and initial SAR studies
Arkivoc. 2010 :175-188
PMID: ISI:000282479600015 PMCID: PMC3106444
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. National Institutes of Health [NIAID R21AI063324, R43AI084224, NCI T32CA009035, P30CA006927] We thank Drs. Trevor Selwood and Sarah Lawrence of the Fox Chase Cancer Center. We acknowledge the following National Institutes of Health grant support of this work: NIAID R21AI063324 (EKJ) and R43AI084224 (ABR), and NCI T32CA009035 (ICR) and P30CA006927 (FCCC). 26 Arkat usa inc; c/o alan r katritzky, univ florida, dept chemistry, po box 117200 Part 8 658gx