Why a benign mutation kills enzyme activity. Structure-based analysis of the A176V mutant of Saccharomyces cerevisiae L-asparaginase I

• Autorzy: Bonthron D. T. , Jaskolski M.
• Języki publikacji: EN

Abstrakty

EN

A conservative and apparently harmless AI76V mutation in intracellular S. cerevisiae L-asparaginase (ScerAI) completely abolishes the enzyme activity. Sequence and structural comparisons with type II bacterial L-asparaginases show that the mutated residue is in a very conservative region and plays a vital role in the cohesion of functional tetramers of these enzymes through participation in side-chain...main-chain (Ser) Oy...O (Ala) hydrogen bonds across the tetramer interface. The fact that bacterial L-asparaginases of type I show less conservation in this region suggests that they may have different quaternary structure while adopting the subunit fold and intimate dimer architecture of type II enzymes. A comparison of all available sequences of microbial L- asparaginases confirms that separate intra- and extra-cellular enzymes evolved in prokaryotes and eukaryotes independently. However, an analysis of the available complete genome sequences reveals a surprising fact that Haemophi­lus influenzae possesses only a type II asparaginase while the archaebacterium Methanococcus jannaschii has a type I gene, but not a type II.

Słowa kluczowe

EN

molecular modelling; L-asparaginase; leukemia; sequence analysis; enzyme activity; mutation; mutant; Saccharomyces cerevisiae

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1997
• Tom: 44
• Numer: 3
• Opis fizyczny: p.491-504,fig.

Twórcy

autor

Bonthron D. T.

• University of Edinburgh, Edinburgh, EH4 2XU, U.K.

autor

Jaskolski M.

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