A study of Rose Bengal against a 2-keto-3-deoxy-d-manno-octulosonate cytidylyltransferase as an antibiotic candidate. (1st January 2020)

• Record Type: Journal Article
• Authors: Kim, Suwon; Jo, Seri; Kim, Mi-Sun; Shin, Dong Hae
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 35:Number 1(2020)
• Page Start: 1414
• Page End: 1421
• Publication Date: 2020-01-01
• Subjects: CMP-2-keto-3-deoxy-d-manno-octulosonic acid biosynthesis pathway -- 2-keto-3-deoxy-d-manno-octulosonate cytidylyltransferase (KdsB) -- melioidosis -- multi-drug resistance -- Rose Bengal; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2020.1751150
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Frequent occurrences of multi-drug resistance of pathogenic Gram-negative bacteria threaten human beings. The CMP-2-keto-3-deoxy-d - manno -octulosonic acid biosynthesis pathway is one of the new targets for antibiotic design. 2-Keto-3-deoxy-d - manno -octulosonate cytidylyltransferase (KdsB) is the key enzyme in this pathway. KdsB proteins from Burkholderia pseudomallei ( Bp ), B. thailandensis ( Bt ), Pseudomonas aeruginosa ( Pa ), and Chlamydia psittaci ( Cp ) have been assayed to find inhibitors. Interestingly, Rose Bengal (4, 5, 6, 7-tetrachloro-2′, 4′, 5′, 7′-tetraiodofluorescein) was turned out to be an inhibitor of three KdsBs ( Bp KdsB, Bt KdsB, and Pa KdsB) with promising IC50 values and increased thermostability. The inhibitory enzyme kinetics of Rose Bengal revealed that it is competitive with 2-keto-3-deoxy- manno -octulosonic acid (KDO) but non-competitive against cytidine 5′-triphosphate (CTP). Induced-fit docking analysis of Pa KdsB revealed that Arg160 and Arg185 together with other interactions in the substrate binding site seemed to play an important role in binding with Rose Bengal. We suggest that Rose Bengal can be used as the scaffold to develop potential antibiotics.