Homology modeling of Mycobacterium tuberculosis 2C-methyl-D-erythritol-4-phosphate cytidylyltransferase, the third enzyme in the MEP pathway for isoprenoid biosynthesis.

Journal of Molecular Modeling
C Obiol-PardoSantiago Imperial

Abstract

Tuberculosis is one of the leading infectious diseases in humans. Discovering new treatments for this disease is urgently required, especially in view of the emergence of multiple drug resistant organisms and to reduce the total duration of current treatments. The synthesis of isoprenoids in Mycobacterium tuberculosis has been reported as an interesting pathway to target, and particular attention has been focused on the methylerythritol phosphate (MEP) pathway comprising the early steps of isoprenoid biosynthesis. In this context we have studied the enzyme 2C-methyl-D-erythritol-4-phosphate cytidylyltransferase (CMS), the third enzyme in the MEP pathway, since the lack of a resolved structure of this protein in M. tuberculosis has seriously limited its use as a drug target. We performed homology modeling of M. tuberculosis CMS in order to provide a reliable model for use in structure-based drug design. After evaluating the quality of the model, we performed a thorough study of the catalytic site and the dimerization interface of the model, which suggested the most important sites (conserved and non-conserved) that could be useful for drug discovery and mutagenesis studies. We found that the metal coordination of CDP-methyleryth...Continue Reading

References

Jun 1, 1977·Journal of General Microbiology·M D CollinsD E Minnikin
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Sep 1, 1993·Protein Science : a Publication of the Protein Society·C Colovos, T O Yeates
Mar 29, 1996·The Journal of Biological Chemistry·K MikusováP J Brennan
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Nov 5, 1997·Science·J C Sacchettini, C D Poulter
Jan 1, 1997·Methods in Enzymology·D EisenbergJ U Bowie
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·B M LangeR Croteau
Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·F RohdichM H Zenk
Dec 2, 1999·Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America·D R Burwen, M F Seawright
Oct 25, 2000·Protein Science : a Publication of the Protein Society·A FiserA Sali
Apr 24, 2001·American Journal of Respiratory and Critical Care Medicine·R J O'Brien, P P Nunn
Oct 8, 2003·Current Pharmaceutical Biotechnology·C A Testa, M J Brown
Feb 14, 2004·Lancet·Joia S MukherjeeKwonjune J Seung
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Jun 25, 2004·Nucleic Acids Research·Matthias Heinig, Dmitrij Frishman
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jul 29, 2004·Current Pharmaceutical Design·M Rodríguez-Concepción
Jul 29, 2004·Drug Discovery Today·Alexander HillischRolf Hilgenfeld
Nov 9, 2004·Bioorganic Chemistry·Philip J Proteau
Oct 8, 2005·Journal of Structural and Functional Genomics·Scott A Lesley, Ian A Wilson
May 23, 2007·Nucleic Acids Research·Markus Wiederstein, Manfred J Sippl
Aug 10, 2007·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Kate Traynor
Sep 18, 2007·Journal of Computer-aided Molecular Design·Nidhi SinghChristopher R McCurdy
Jan 29, 2008·Recent Patents on Anti-infective Drug Discovery·Marcus Vinícius Nora de Souza
Apr 23, 2008·Current Protocols in Bioinformatics·Narayanan EswarAndrej Sali
Dec 17, 2008·Journal of Bacteriology·Stefanie BaurWaldemar Vollmer
Dec 30, 2008·Journal of Molecular Graphics & Modelling·Cristian Obiol-Pardo, Jaime Rubio-Martinez
Mar 27, 2009·Journal of Chemical Information and Modeling·Xinglong ZhangRenxiao Wang

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Citations

Mar 19, 2014·Journal of Molecular Graphics & Modelling·Cristian Obiol-PardoJaime Rubio-Martinez
Feb 21, 2019·Journal of Computer-aided Molecular Design·P ChellapandiA Prisilla

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