Bonthron D T, Jaskólski M
Human Genetics Unit, University of Edinburgh, Western General Hospital, UK.
Acta Biochim Pol. 1997;44(3):491-504.
A conservative and apparently harmless A176V 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.
酿酒酵母细胞内L-天冬酰胺酶（ScerAI）中一个保守且看似无害的A176V突变完全消除了该酶的活性。与II型细菌L-天冬酰胺酶的序列和结构比较表明，突变残基位于一个非常保守的区域，通过参与跨四聚体界面的侧链……主链（Ser）Oy……O（Ala）氢键，在这些酶的功能性四聚体的凝聚中起关键作用。I型细菌L-天冬酰胺酶在该区域的保守性较低，这一事实表明，它们在采用II型酶的亚基折叠和紧密二聚体结构时，可能具有不同的四级结构。对所有可用的微生物L-天冬酰胺酶序列进行比较证实，细胞内和细胞外的酶在原核生物和真核生物中是独立进化的。然而，对可用的完整基因组序列进行分析后发现了一个惊人的事实，即流感嗜血杆菌仅拥有一种II型天冬酰胺酶，而嗜压甲烷球菌这种古细菌拥有一个I型基因，但没有II型基因。
