Literature DB >> 20975887

Computational genome analyses of metabolic enzymes in Mycobacterium leprae for drug target identification.

Anusuya Shanmugam1, Jeyakumar Natarajan.   

Abstract

Leprosy is an infectious disease caused by Mycobacterium leprae. M. leprae has undergone a major reductive evolution leaving a minimal set of functional genes for survival. It remains non-cultivable. As M. leprae develops resistance against most of the drugs, novel drug targets are required in order to design new drugs. As most of the essential genes mediate several biosynthetic and metabolic pathways, the pathway predictions can predict essential genes. We used comparative genome analysis of metabolic enzymes in M. leprae and H. sapiens using KEGG pathway database and identified 179 non-homologues enzymes. On further comparison of these 179 non-homologous enzymes to the list of minimal set of 48 essential genes required for cell-wall biosynthesis of M. leprae reveals eight common enzymes. Interestingly, six of these eight common enzymes map to that of peptidoglycan biosynthesis and they all belong to Mur enzymes. The machinery for peptidoglycan biosynthesis is a rich source of crucial targets for antibacterial chemotherapy and thus targeting these enzymes is a step towards facilitating the search for new antibiotics.

Entities:  

Keywords:  Comparative genomics; Leprosy; M. leprae; Mur enzymes

Year:  2010        PMID: 20975887      PMCID: PMC2951640          DOI: 10.6026/97320630004392

Source DB:  PubMed          Journal:  Bioinformation        ISSN: 0973-2063


  11 in total

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Authors:  Brian Fritz; Gregory A Raczniak
Journal:  BioDrugs       Date:  2002       Impact factor: 5.807

Review 2.  Genetic strategies for antibacterial drug discovery.

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Journal:  Nat Rev Genet       Date:  2003-06       Impact factor: 53.242

3.  Postgenomic approach to identify novel Mycobacterium leprae antigens with potential to improve immunodiagnosis of infection.

Authors:  Annemieke Geluk; Michèl R Klein; Kees L M C Franken; Krista E van Meijgaarden; Brigitte Wieles; Kelly Cristina Pereira; Samira Bührer-Sékula; Paul R Klatser; Patrick J Brennan; John S Spencer; Diana L Williams; Maria C V Pessolani; Elizabeth P Sampaio; Tom H M Ottenhoff
Journal:  Infect Immun       Date:  2005-09       Impact factor: 3.441

4.  A novel genomics approach for the identification of drug targets in pathogens, with special reference to Pseudomonas aeruginosa.

Authors:  Kishore R Sakharkar; Meena K Sakharkar; Vincent T K Chow
Journal:  In Silico Biol       Date:  2004

5.  Multidrug resistant Mycobacterium leprae from patients with leprosy.

Authors:  S Maeda; M Matsuoka; N Nakata; M Kai; Y Maeda; K Hashimoto; H Kimura; K Kobayashi; Y Kashiwabara
Journal:  Antimicrob Agents Chemother       Date:  2001-12       Impact factor: 5.191

Review 6.  [The Mycobacterium leprae genome: from sequence analysis to therapeutic implications].

Authors:  N Honore
Journal:  Med Trop (Mars)       Date:  2002

Review 7.  The continuing challenges of leprosy.

Authors:  D M Scollard; L B Adams; T P Gillis; J L Krahenbuhl; R W Truman; D L Williams
Journal:  Clin Microbiol Rev       Date:  2006-04       Impact factor: 26.132

Review 8.  Natural and acquired macrolide resistance in mycobacteria.

Authors:  F Doucet-Populaire; K Buriánková; J Weiser; J-L Pernodet
Journal:  Curr Drug Targets Infect Disord       Date:  2002-12

9.  Comparative studies of the cell structures of Mycobacterium leprae and M. tuberculosis using the electron microscopy freeze-substitution technique.

Authors:  Akemi Takade; Akiko Umeda; Masanori Matsuoka; Shin-ichi Yoshida; Masahiro Nakamura; Kazunobu Amako
Journal:  Microbiol Immunol       Date:  2003       Impact factor: 1.955

Review 10.  The genome of Mycobacterium leprae: a minimal mycobacterial gene set.

Authors:  V D Vissa; P J Brennan
Journal:  Genome Biol       Date:  2001-08-03       Impact factor: 13.583

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  8 in total

1.  Comparative modeling of UDP-N-acetylmuramoyl-glycyl-D-glutamate-2, 6-diaminopimelate ligase from Mycobacterium leprae and analysis of its binding features through molecular docking studies.

Authors:  Anusuya Shanmugam; Jeyakumar Natarajan
Journal:  J Mol Model       Date:  2011-04-15       Impact factor: 1.810

2.  Homology modeling and docking analyses of M. leprae Mur ligases reveals the common binding residues for structure based drug designing to eradicate leprosy.

Authors:  Anusuya Shanmugam; Jeyakumar Natarajan
Journal:  J Mol Model       Date:  2011-11-19       Impact factor: 1.810

Review 3.  In silico Methods for Identification of Potential Therapeutic Targets.

Authors:  Xuting Zhang; Fengxu Wu; Nan Yang; Xiaohui Zhan; Jianbo Liao; Shangkang Mai; Zunnan Huang
Journal:  Interdiscip Sci       Date:  2021-11-26       Impact factor: 3.492

4.  Finding Potential Therapeutic Targets against Shigella flexneri through Proteome Exploration.

Authors:  Mohammad Uzzal Hossain; Md Arif Khan; Abu Hashem; Md Monirul Islam; Mohammad Neaz Morshed; Chaman Ara Keya; Md Salimullah
Journal:  Front Microbiol       Date:  2016-11-22       Impact factor: 5.640

5.  Comparative genomics analysis of Mycobacterium ulcerans for the identification of putative essential genes and therapeutic candidates.

Authors:  Azeem Mehmood Butt; Izza Nasrullah; Shifa Tahir; Yigang Tong
Journal:  PLoS One       Date:  2012-08-13       Impact factor: 3.240

6.  Identification and characterization of potential therapeutic candidates in emerging human pathogen Mycobacterium abscessus: a novel hierarchical in silico approach.

Authors:  Buvaneswari Shanmugham; Archana Pan
Journal:  PLoS One       Date:  2013-03-19       Impact factor: 3.240

7.  Exoproteome and secretome derived broad spectrum novel drug and vaccine candidates in Vibrio cholerae targeted by Piper betel derived compounds.

Authors:  Debmalya Barh; Neha Barve; Krishnakant Gupta; Sudha Chandra; Neha Jain; Sandeep Tiwari; Nidia Leon-Sicairos; Adrian Canizalez-Roman; Anderson Rodrigues dos Santos; Syed Shah Hassan; Síntia Almeida; Rommel Thiago Jucá Ramos; Vinicius Augusto Carvalho de Abreu; Adriana Ribeiro Carneiro; Siomar de Castro Soares; Thiago Luiz de Paula Castro; Anderson Miyoshi; Artur Silva; Anil Kumar; Amarendra Narayan Misra; Kenneth Blum; Eric R Braverman; Vasco Azevedo
Journal:  PLoS One       Date:  2013-01-30       Impact factor: 3.240

8.  An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets.

Authors:  Pablo Ivan Pereira Ramos; Darío Fernández Do Porto; Esteban Lanzarotti; Ezequiel J Sosa; Germán Burguener; Agustín M Pardo; Cecilia C Klein; Marie-France Sagot; Ana Tereza R de Vasconcelos; Ana Cristina Gales; Marcelo Marti; Adrián G Turjanski; Marisa F Nicolás
Journal:  Sci Rep       Date:  2018-07-17       Impact factor: 4.379

  8 in total

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