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A study of Rose Bengal against a 2-keto-3-deoxy-d-manno-octulosonate cytidylyltransferase as an antibiotic candidate

Title
A study of Rose Bengal against a 2-keto-3-deoxy-d-manno-octulosonate cytidylyltransferase as an antibiotic candidate
Authors
Kim S.Jo S.Kim M.-S.Shin D.H.
Ewha Authors
신동해김수원김미선
SCOPUS Author ID
신동해scopus; 김수원scopus
Issue Date
2020
Journal Title
Journal of enzyme inhibition and medicinal chemistry
ISSN
1475-6374JCR Link
Citation
Journal of enzyme inhibition and medicinal chemistry vol. 35, no. 1, pp. 1414 - 1421
Keywords
2-keto-3-deoxy-d-manno-octulosonate cytidylyltransferase (KdsB)CMP-2-keto-3-deoxy-d-manno-octulosonic acid biosynthesis pathwaymelioidosismulti-drug resistanceRose Bengal
Publisher
NLM (Medline)
Indexed
SCOPUS scopus
Document Type
Article
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 (BpKdsB, BtKdsB, and PaKdsB) 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 PaKdsB 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.
DOI
10.1080/14756366.2020.1751150
Appears in Collections:
약학대학 > 약학과 > Journal papers
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