7AJR

Virtual screening approach leading to the identification of a novel and tractable series of Pseudomonas aeruginosa elastase inhibitors

This is a non-PDB format compatible entry.

Summary for 7AJR

• Entry DOI: 10.2210/pdb7ajr/pdb
• Descriptor: Keratinase KP2, 2-[2-(1,3-benzothiazol-2-ylmethylcarbamoyl)-1,3-dihydroinden-2-yl]ethanoic acid, ZINC ION, ... (5 entities in total)
• Functional Keywords: pseudomonas aeruginosa, elastase, inhibitors, hydrolase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 33703.44

Authors

Leiris, S.,Davies, D.T.,Sprinsky, N.,Castandet, J.,Behria, L.,Bodnarchuk, M.S.,Sutton, J.M.,Mullins, T.M.G.,Jones, M.W.,Forrest, A.K.,Pallin, T.D.,Karunakar, P.,Martha, S.K.,Parusharamulu, B.,Ramula, R.,Kotha, V.,Pottabathini, N.,Pothukanuri, S.,Lemonnier, M.,Everett, M. (deposition date: 2020-09-29, release date: 2021-02-10, Last modification date: 2024-10-16)

Primary citation

Leiris, S.,Davies, D.T.,Sprynski, N.,Castandet, J.,Beyria, L.,Bodnarchuk, M.S.,Sutton, J.M.,Mullins, T.M.G.,Jones, M.W.,Forrest, A.K.,Pallin, T.D.,Karunakar, P.,Martha, S.K.,Parusharamulu, B.,Ramula, R.,Kotha, V.,Pottabathini, N.,Pothukanuri, S.,Lemonnier, M.,Everett, M.
Virtual Screening Approach to Identifying a Novel and Tractable Series of Pseudomonas aeruginosa Elastase Inhibitors.
Acs Med.Chem.Lett., 12:217-227, 2021

PubMed Abstract: Novel therapies are required to treat chronic bacterial infections in cystic fibrosis (CF) sufferers. The most common pathogen responsible for these infections is , which persists within the lungs of CF sufferers despite intensive antibiotic treatment. elastase (also known as LasB or pseudolysin) is a key virulence determinant that contributes to the pathogenesis and persistence of infections in CF patients. The crucial role of LasB in pseudomonal virulence makes it a good target for the development of an adjuvant drug for CF treatment. Herein we discuss the discovery of a new series of LasB inhibitors by virtual screening and computer assisted drug design (CADD) and their optimization leading to compounds and ( = 0.16 μM and 0.12 μM, respectively).

PubMed: 33603968
DOI: 10.1021/acsmedchemlett.0c00554

Experimental method

X-RAY DIFFRACTION (1.75 Å)