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Wyniki wyszukiwania dla: homoaconitase
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Phenotypic consequences of LYS4 gene disruption in Candida albicans
PublikacjaA BLAST search of the Candida Genome Database with the Saccharomyces cerevisiae LYS4 sequence known to encode homoaconitase (HA) revealed ORFs 19.3846 and 19.11327. Both alleles of the LYS4 gene were sequentially disrupted in Candida albicans BWP17 cells using PCR-based methodology. The null lys4Δ mutant exhibited lysine auxotrophy in minimal medium but was able to grow in the presence of L-Lys and α-aminoadipate, an intermediate...
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Antifungal Activity of Homoaconitate and Homoisocitrate Analogs
PublikacjaThirteen structural analogs of two initial intermediates of the L-alpha-aminoadipate pathway of L-lysine biosynthesis in fungi have been designed and synthesized, including fluoro- and epoxy-derivatives of homoaconitate and homoisocitrate. Some of the obtainedcompounds exhibited at milimolar range moderate enzyme inhibitory properties against homoaconitase and/or homoisocitrate dehydrogenase of Candida albicans. The structural...
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Consequences of lysine auxotrophy for Candida albicans adherence and biofilm formation
PublikacjaA number of factors are known to be involved in Candida albicans virulence, although biofilm development on the surfaces of indwelling medical devices is considered to promote superficial or systemic disease. Based on previously reported up-regulation of saccharopine and acetyllysine in biofilm cells and activation of the lysine biosynthesis/degradation pathway, we investigated...
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Enzymes of the lysine biosynthetic pathway as targets for antifungals ?
PublikacjaSystemic infections caused by human pathogenic fungi in immunocompromized patients continue to be one of the important clinical problems. Limited availability of safe and efficacious antifungal chemotherapeutics and emerging resistance to existing drugs stimulates search for novel molecular targets for antifungals. The α-aminoadipate pathway (AAP) of L-lysine biosynthesis is unique in fungi and thus has been so far considered...
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Phenotypic consequences of the LYS4 gene disruption in Candida albicans
PublikacjaThe main scientific purpose of our studies was to verify the hypothesis that homoaconitase (HA) from Candida albicans, an enzyme catalyzing a second step of the α-aminoadipate pathway (AAP) of L-Lys biosynthesis may become a new target for antifungal chemotherapy. Previous studies indicated that the A. fumigatus mutant lacking the functional lysF gene, encoding HA, exhibited attenuated virulence in a low-dose mouse infection model...