Mycobacterium tuberculosis chorismate mutase: A potential target for TB. Issue 6 (15th March 2017)

• Record Type: Journal Article
• Authors: Khanapur, Manjulatha; Alvala, Mallika; Prabhakar, Maddela; Shiva Kumar, K.; Edwin, R.K.; Sri Saranya, P.S.V.K.; Patel, Raj Kumar; Bulusu, Gopalakrishnan; Misra, P.; Pal, Manojit
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 6(2017)
• Page Start: 1725
• Page End: 1736
• Publication Date: 2017-03-15
• Subjects: Tuberculosis -- Mycobacterium tuberculosis -- Chorismate mutase -- Inhibitors; BsCM Bacillus subtilis chorismate mutase -- CM chorismate mutase -- DAHP 3-deoxy-d-arabinoheptulosonate 7-phosphate -- EcCM Escherichia coli chorismate mutase -- HIV/AIDS human Immunodeficient virus/acquired immune deficiency syndrome -- IC50 half maximal inhibitory concentration -- Kcat turnover rate of enzyme -- Km Michaleis-Menten constant -- MDR multi drug resistance -- MtbCM intracellular chorismate mutase of Mycobacterium tuberculosis -- *MtbCM secreted chorismate mutase of Mycobacterium tuberculosis -- MtbCM-MtbDS MtbCM in complex with DAHP synthase -- PDB Protein Data Bank -- ScCM Saccharomyces cerevisiae chorismate mutase -- TB tuberculosis -- Tm melting temperature -- TSA transition state analogue; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.02.001
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Mycobacterium tuberculosis chorismate mutase ( Mtb CM) catalyzes the rearrangement of chorismate to prephenate in the shikimate biosynthetic pathway to form the essential amino acids, phenylalanine and tyrosine. Two genes encoding chorismate mutase have been identified in Mtb . The secretory form, ∗ Mtb CM (encoded by Rv1885c) is assumed to play a key role in pathogenesis of tuberculosis. Also, the inhibition of Mtb CM may hinder the supply of nutrients to the organism. Indeed, the existence of chorismate mutase (CM) in bacteria, fungi and higher plants but not in human and low sequence homology among known CM makes it an interesting target for the discovery of anti-tubercular agents. The present article mainly focuses on the recent developments in the structure, function and inhibition of Mtb CM. The understanding of various aspects of Mtb CM as presented in the current article may facilitate the design and subsequent chemical synthesis of new inhibitors against ∗ Mtb CM, that could lead to the discovery and development of novel and potent anti-tubercular agents in future.