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Mycobacterium tuberculosis chorismate mutase: A potential target for TB
被引:38
作者:
Khanapur, Manjulatha
[1
]
Alvala, Mallika
[2
]
Prabhakar, Maddela
[1
]
Kumar, K. Shiva
[3
]
Edwin, R. K.
[2
]
Saranya, P. S. V. K. Sri
[4
]
Patel, Raj Kumar
[4
]
Bulusu, Gopalakrishnan
[4
,5
]
Misra, P.
[2
]
Pal, Manojit
[1
]
机构:
[1] Univ Hyderabad Campus, Dr Reddys Inst Life Sci, Dept Med Chem, Hyderabad 500046, Andhra Pradesh, India
[2] Univ Hyderabad Campus, Dr Reddys Inst Life Sci, Dept Biol, Hyderabad 500046, Andhra Pradesh, India
[3] Osmania Univ, Dept Chem, Hyderabad 500007, Andhra Pradesh, India
[4] Univ Hyderabad Campus, Dr Reddys Inst Life Sci, Dept Mol Modeling, Hyderabad 500046, Andhra Pradesh, India
[5] Tata Consultancy Serv Ltd, Life Sci Div, TCS Innovat Labs Hyderabad, Hyderabad 500081, Andhra Pradesh, India
关键词:
Tuberculosis;
Mycobacterium tuberculosis;
Chorismate mutase;
Inhibitors;
TRANSITION-STATE ANALOG;
IN-VITRO EVALUATION;
AROMATIC-AMINO-ACIDS;
CRYSTAL-STRUCTURE;
PREPHENATE DEHYDROGENASE;
CLAISEN REARRANGEMENT;
CATALYTIC MECHANISM;
BACILLUS-SUBTILIS;
SHIKIMATE PATHWAY;
DRUG DISCOVERY;
D O I:
10.1016/j.bmc.2017.02.001
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
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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页码:1725 / 1736
页数:12
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