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Mycobacterium tuberculosis chorismate mutase: A potential target for TB

Journal

BIOORGANIC & MEDICINAL CHEMISTRY
Volume 25, Issue 6, Pages 1725-1736

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2017.02.001

Keywords

Tuberculosis; Mycobacterium tuberculosis; Chorismate mutase; Inhibitors

Funding

  1. Dr. Reddy's Institute of Life Sciences
  2. DBT, New Delhi, India [BT/PR12817/COE/34/23/2015]

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Mycobacterium tuberculosis chorismate mutase (MtbCM) 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,(*)MtbCM (encoded by Rv1885c) is assumed to play a key role in pathogenesis of tuberculosis. Also, the inhibition of MtbCM 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 MtbCM. The understanding of various aspects of MtbCM as presented in the current article may facilitate the design and subsequent chemical synthesis of new inhibitors against (*)MtbCM, that could lead to the discovery and development of novel and potent anti-tubercular agents in future. (C) 2017 Elsevier Ltd. All rights reserved.

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