VSE knjižnice (vzajemna bibliografsko-kataložna baza podatkov COBIB.SI)
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  • Evolution of allosteric citrate bindings sites on 6-phosphofructo-1-kinase [Elektronski vir] : evolution of 6-phosphofructo-1-kinase
    Usenik, Aleksandra ; Legiša, Matic
    As an important part of metabolism, metabolic flux through the glycolytic pathway is tight1y regulated. The most complex control is exerted on 6-phosphofructo-l-kinase (PFKl) level; this control ... overrules the regulatory role of other allosteric enzymes. Among other effectors, citrate has been reported to playavital role in the suppression ofthis enzyme's activity. In eukaryotes, allosteric biding sites for citrate are scattered through both theN- and the CCtermini of the enzyme. These sites have evolved from the phosphoenolpyruvate/ADP binding site ofbacterial PFKl due to the processes of duplication and tandem fusion ofprokaryotic ancestor gene followed by the divergence of the catalytic and effect or binding sites. Stricter inhibition of the PFKl enzyme was needed during the evolution of multi-cellular organisms, and the most stringent control of PFKl by citrate occurs in vertebrates. By substituting a single amino acid (K557 or K6l7) in an allosteric binding site in the C-terminus of human musc1e type PFK-M with a residue found in the corresponding site of a fungal enzyme, the inhibitory effect of citrate was attenuated. Moreover, these single mutations enabled growth of E.coli transformants encoding mutated human PFK-M in a glucose-containing medium that did not support the growth of E.coli transformed with native human PFK-M. Substitution of another residue at the citrate-binding locus (D59lV) ofhurnan PFK-M resulted in the complete loss of activity. Detailed analyses revealed that the mutated PFK-M subunits formed dimers but were unable to associate into the active tetrameric holoenzyrne. These results suggest that stricter control over glycolytic flux developed in metazoans, whose somatic cells are largely characterized by slow proliferation.
    Vir: PloS one [Elektronski vir]. - ISSN 1932-6203 (Vol. 5, iss. 11, 2010, 8 str.)
    Vrsta gradiva - e-članek
    Leto - 2010
    Jezik - angleški
    COBISS.SI-ID - 4531226
    DOI

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