@article {46659,
	title = {NADP-dependent glutamate dehydrogenases in a dimorphic zygomycete Benjaminiella poitrasii: purification, characterization and their evaluation as an antifungal drug target},
	journal = {Biochimica Et Biophysica Acta-General Subjects},
	volume = {1864},
	year = {2020},
	month = {NOV},
	pages = {129696},
	type = {Article},
	abstract = {<p>Background: It has been reported that the genes coding for NADP-dependent glutamate dehydrogenases (NADP-GDHs) showed a cause-effect relationship with Yeast-Hypha (Y-H) reversible transition in a zygomycete Benjaminiella poitrasii. As Y-H transition is significant in human pathogenic fungi for their survival and proliferation in the host, the NADP-GDHs can be explored as antifungal drug targets. Methods: The yeast-form specific BpNADPGDH I and hyphal-form specific BpNADPGDH II of B. poitrasii were purified by heterologous expression in E. coll. BL-21 cells and characterized. The structural analogs of L-glutamate, dimethyl esters of isophthalic acid (DMIP) and its derivatives were designed, synthesized and screened for inhibition of NADP-GDH activity as well as Y-H transition in B. poitrasii, and also in human pathogenic Candida albicans strains. Results: The BpNADPGDH I and BpNADPGDH II were found to be homo-hexameric proteins with native molecular mass of 282 kDa and 298 kDa, respectively and subunit molecular weights of 47 kDa and 49 kDa, respectively. Besides the distinct kinetic properties, BpNADPGDH I and BpNADPGDH II were found to be regulated by cAMP-dependent- and Calmodulin (CaM) dependent- protein kinases, respectively. The DMIP compounds showed a more pronounced effect on H-form specific BpNADPGDH II and inhibited Y-H transition as well as growth in B. poitrasii and C. albicans strains. Conclusion: The present study will be useful to design and develop antifungal drugs against dimorphic human pathogens using glutamate dehydrogenase as a target. Significance: Glutamate dehydrogenases can be explored as a target against human pathogenic fungi.</p>
},
	keywords = {Antifungal compound, Benjaminiella poitrasii, Candida albicans, Dimethyl esters and amides of isophthalic acid, dimorphism, Enzyme inhibition, NADP-glutamate dehydrogenases},
	issn = {0304-4165},
	doi = {10.1016/j.bbagen.2020.129696},
	author = {Pathan, Ejaj K. and Kulkarni, Anand M. and Prasanna, Nallaballe V. L. and Ramana, V, Chepuri and Deshpande, V, Mukund}
}
