02706nas a2200277   4500008004100000022001400041245017600055210006900231260000800300300001100308490000900319520169400328653002402022653002802046653002102074653005102095653001502146653002202161653003402183100002102217700002402238700003202262700000502294700000502299856012402304       2020                        eng d  a0304-416500aNADP-dependent glutamate dehydrogenases in a dimorphic zygomycete Benjaminiella poitrasii: purification, characterization and their evaluation as an antifungal drug target0 aNADPdependent glutamate dehydrogenases in a dimorphic zygomycete  cNOV  a1296960 v18643 a<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>
10aAntifungal compound10aBenjaminiella poitrasii10aCandida albicans10aDimethyl esters and amides of isophthalic acid10adimorphism10aEnzyme inhibition10aNADP-glutamate dehydrogenases1 aPathan, Ejaj, K.1 aKulkarni, Anand, M.1 aPrasanna, Nallaballe, V. L.1 a1 a  uhttps://library.ncl.res.in/content/nadp-dependent-glutamate-dehydrogenases-dimorphic-zygomycete-benjaminiella-poitrasii