A biochemical correlate of dimorphism in a zygomycete Benjaminiella poitrasii: characterization of purified NAD-dependent glutamate dehydrogenase, a target for antifungal agents
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Title |
A biochemical correlate of dimorphism in a zygomycete Benjaminiella poitrasii: characterization of purified NAD-dependent glutamate dehydrogenase, a target for antifungal agents
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Creator |
JOSHI, CV
PATHAN, EK PUNEKAR, NS TUPE, SG KAPADNIS, BP DESHPANDE, MV |
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Subject |
Antifungal agent
Benjaminiella poitrasii Biochemical correlate of dimorphism Candida albicans NAD-GDH activity regulation Yarrowia lipolytica Yeast-hypha reversible transition MORPHOLOGY-ASSOCIATED EXPRESSION YEAST-MYCELIUM TRANSITION SACCHAROMYCES-CEREVISIAE PROTEIN-KINASES BETA-LACTAM PURIFICATION ACID NEUROSPORA FUNGUS INACTIVATION |
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Description |
The fungal organisms, especially pathogens, change their vegetative (Y, unicellular yeast and H, hypha) morphology reversibly for survival and proliferation in the host environment. NAD-dependent glutamate dehydrogenase (NAD-GDH, EC 1.4.1.2) from a non-pathogenic dimorphic zygomycete Benjaminiella poitrasii was previously reported to be an important biochemical correlate of the transition process. The enzyme was purified to homogeneity and characterized. It is a 371 kDa native molecular weight protein made up of four identical subunits. Kinetic studies showed that unlike other NAD-GDHs, it may act as an anabolic enzyme and has more affinity towards 2-oxoglutarate than l-glutamate. Chemical modifications revealed the involvement of single histidine and lysine residues in the catalytic activity of the enzyme. The phosphorylation and dephosphorylation study showed that the NAD-GDH is present in active phosphorylated form in hyphal cells of B. poitrasii. Two of the 1,2,3 triazole linked beta-lactam-bile acid conjugates synthesized in the laboratory (B18, B20) were found to be potent inhibitors of purified NAD-GDH which also significantly affected Y-H transition in B. poitrasii. Furthermore, the compound B20 inhibited germ tube formation during Y-H transition in Candida albicans strains and Yarrowia lipolytica. The possible use of NAD-GDH as a target for antifungal agents is discussed.
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Publisher |
SPRINGER
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Date |
2014-10-16T12:25:35Z
2014-10-16T12:25:35Z 2013 |
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Type |
Article
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Identifier |
ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY, 104(1)25-36
http://dx.doi.org/10.1007/s10482-013-9921-5 http://dspace.library.iitb.ac.in/jspui/handle/100/15541 |
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Language |
en
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