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Reitz AB, Ramirez UD, Stith L, et al. Pseudomonas aeruginosa porphobilinogen synthase assembly state regulators: hit discovery and initial SAR studies. ARKIVOC. 2010;2010:175-188
Reitz, A. B., Ramirez, U. D., Stith, L., Du, Y., Smith, G. R., & Jaffe, E. K. (2010). Pseudomonas aeruginosa porphobilinogen synthase assembly state regulators: hit discovery and initial SAR studies. ARKIVOC : free online journal of organic chemistry, 2010175-188.
Reitz, Allen B, et al. "Pseudomonas aeruginosa porphobilinogen synthase assembly state regulators: hit discovery and initial SAR studies." ARKIVOC : free online journal of organic chemistry vol. 2010 (2010): 175-188.
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.
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ARKIVOC. 2010 Jun;2010:175-188.

Pseudomonas aeruginosa porphobilinogen synthase assembly state regulators: hit discovery and initial SAR studies.

ARKIVOC : free online journal of organic chemistry

Allen B Reitz, Ursula D Ramirez, Linda Stith, Yanming Du, Garry R Smith, Eileen K Jaffe

Affiliations

  1. Fox Chase Chemical Diversity Center, Inc., Pennsylvania Center for Drug Discovery, Pennsylvania Biotechnology Center, Doylestown, PA 18902 USA.

PMID: 21643541 PMCID: PMC3106444

Abstract

Porphobilinogen 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.

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