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Molecular characterization of Mtb-OMP decarboxylase by modeling, docking and dynamic studies

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Abstract

Tuberculosis (TB), the second most deadly disease in the world is caused by Mycobacterium tuberculosis (Mtb). In the present work a unique enzyme of Mtb orotidine 5′ monophosphate decarboxylase (Mtb-OMP Decase) is selected as drug target due to its indispensible role in biosynthesis of pyrimidines. The present work is focused on understanding the structural and functional aspects of Mtb-OMP Decase at molecular level. Due to absence of crystal structure, the 3D structure of Mtb-OMP Decase was predicted by MODELLER9V7 using a known structural template 3L52. Energy minimization and refinement of the developed 3D model was carried out with Gromacs 3.2.1 and the optimized homology model was validated by PROCHECK,WHAT-IF and PROSA2003. Further, the surface active site amino acids were quantified by WHAT-IF pocket. The exact binding interactions of the ligands, 6-idiouridine 5′ monophosphate and its designed analogues with the receptor Mtb-OMP Decase were predicted by docking analysis with AUTODOCK 4.0. This would be helpful in understanding the blockade mechanism of OMP Decase and provide a candidate lead for the discovery of Mtb-OMP Decase inhibitors, which may bring insights into outcome new therapy to treat drug resistant Mtb.

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Authors and Affiliations

  1. Department of Biotechnology, Sri Krishnadevaraya University, Anantapur, 260003, India

    P. Madhusudana & C. M. Anuradha

  2. Department of Biotechnology, Acharya Nagarjuna University, Guntur, 522510, India

    P. Madhusudana, K. R. S. Sambasiva Rao & Sudhakar Poda

  3. BIF, Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, 260003, India

    P. Madhusudana, B. Babajan, M. Chaitanya, Rajasekar Chikati & Chitta Suresh Kumar

  4. Primary Health Centre, Narpal, Anantapur, 515425, India

    C. Shobharani

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  1. P. Madhusudana
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  2. B. Babajan
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  4. C. M. Anuradha
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Correspondence to C. M. Anuradha or Chitta Suresh Kumar.

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Madhusudana, P., Babajan, B., Chaitanya, M. et al. Molecular characterization of Mtb-OMP decarboxylase by modeling, docking and dynamic studies. Interdiscip Sci Comput Life Sci 4, 142–152 (2012). https://doi.org/10.1007/s12539-012-0127-8

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  • DOI: https://doi.org/10.1007/s12539-012-0127-8

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