caa a22 4500 605512612 CHVBK 20210128100656.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00894-015-2630-4 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2630-4 Mechanistic insights from molecular dynamic simulation of Rv0045c esterase in Mycobacterium tuberculosis [Elektronische Daten] [Durairaj Sherlin, Sharmila Anishetty] Rv0045c is an esterase involved in lipid metabolism of Mycobacterium tuberculosis. It belongs to the α/β hydrolase family. In the current study, we performed sequence- and structure-based analysis of Rv0045c followed by molecular dynamics (MD) simulation for 100ns to investigate conformational changes in the enzyme. Sequence analysis revealed that this enzyme is possibly a hormone-sensitive lipase. Further, through structural analysis, a putative catalytic tetrad containing "Ser-Asp-Ser-His” and residues involved in the formation of an oxyanion hole were identified. MD simulation of Rv0045c revealed a conformational transition from an open to a closed state. The active site pocket was found to be gated by four loops. The potential role of the cap domain and the mobile histidine is discussed. From the simulation, we see that the conformational changes mimic the different stages in the reaction mechanism of Rv0045c. These results support the hypothesis that free enzyme simulation encompasses all the conformations necessary for the different stages of catalysis. Our findings add to the growing knowledge of an important family of esterases in Mycobacterium tuberculosis. Graphical Abstract Sequence and structural analysis of Rv0045c Springer-Verlag Berlin Heidelberg, 2015 Esterase nationallicence Catalytic tetrad nationallicence Conformational transition nationallicence Hormone-sensitive lipase nationallicence Histidine flipping nationallicence Sherlin Durairaj Center for Biotechnology, Anna University, 600 025, Chennai, India aut Anishetty Sharmila Center for Biotechnology, Anna University, 600 025, Chennai, India aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/4(2015-04-01), 1-8 1610-2940 21:4<1 2015 21 894 https://doi.org/10.1007/s00894-015-2630-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2630-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sherlin Durairaj Center for Biotechnology, Anna University, 600 025, Chennai, India aut NATIONALLICENCE 700 1- Anishetty Sharmila Center for Biotechnology, Anna University, 600 025, Chennai, India aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/4(2015-04-01), 1-8 1610-2940 21:4<1 2015 21 894