caa a22 4500 605501483 CHVBK 20210128100601.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00253-015-6502-8 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6502-8 Biochemical and functional characterizations of tyrosine phosphatases from pathogenic and nonpathogenic mycobacteria: indication of phenyl cyclopropyl methyl-/phenyl butenyl azoles as tyrosine phosphatase inhibitors [Elektronische Daten] [Aditi Chatterjee, Sapna Pandey, Pramod Singh, Navendu Pathak, Niyati Rai, Ravishankar Ramachandran, Rama Tripathi, Kishore Srivastava] Tyrosine phosphorylation is one of the most common means of posttranslational modifications which can generate novel recognition motifs for protein interactions and thereafter affecting cellular localization, protein stability, and enzyme activity. Mycobacterium tuberculosis (Mtb) possesses a wide range of signal transduction systems, including two protein tyrosine phosphatases (PtpA and PtpB). Since functional diversities between protein tyrosine phosphatases (PTPases) are illustrated by regulatory domains and subunits, we have characterized the nature of tyrosine phosphatases from slow-grower pathogenic species Mtb and from fast-grower nonpathogenic species Mycobacterium smegmatis (MS). The findings delineate that the enzymes present in MS have significantly lesser phosphatase activity than PTPases of Mtb as evidenced by low K cat/K m of recombinantly expressed proteins. The K cat/K m for Mtb PtpA was 500-1000-fold higher than MS PTPases. We have designed and synthesized phenyl cyclopropyl methyl-/phenyl butenyl azoles which inhibit growth of mycobacteria, in culture and in macrophages. The mechanism of efficacy of these compounds against mycobacteria was identified and suggested that the inhibition may possibly be mediated via the targeting of Mtb tyrosine phosphatase. The results further added that these compounds exclusively inhibit PtpA of Mtb. Springer-Verlag Berlin Heidelberg, 2015 Azoles nationallicence Mycobacteria nationallicence Tyrosine phosphatase nationallicence HTS nationallicence Target nationallicence Chatterjee Aditi Division of Microbiology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut Pandey Sapna Division of Microbiology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut Singh Pramod Division of Microbiology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut Pathak Navendu Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut Rai Niyati Division of Molecular Structural Biology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut Ramachandran Ravishankar Division of Molecular Structural Biology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut Tripathi Rama Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut Srivastava Kishore Division of Microbiology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/18(2015-09-01), 7539-7548 0175-7598 99:18<7539 2015 99 253 https://doi.org/10.1007/s00253-015-6502-8 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/s00253-015-6502-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chatterjee Aditi Division of Microbiology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut NATIONALLICENCE 700 1- Pandey Sapna Division of Microbiology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut NATIONALLICENCE 700 1- Singh Pramod Division of Microbiology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut NATIONALLICENCE 700 1- Pathak Navendu Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut NATIONALLICENCE 700 1- Rai Niyati Division of Molecular Structural Biology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut NATIONALLICENCE 700 1- Ramachandran Ravishankar Division of Molecular Structural Biology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut NATIONALLICENCE 700 1- Tripathi Rama Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut NATIONALLICENCE 700 1- Srivastava Kishore Division of Microbiology, CSIR-Central Drug Research Institute, 226 031, Lucknow, India aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/18(2015-09-01), 7539-7548 0175-7598 99:18<7539 2015 99 253