A mechanistic rationalisation for the substrate specificity of recombinant mammalian 4-hydroxyphenylpyruvate dioxygenase (4-HPPD)

被引:53
作者
Crouch, NP [1 ]
Adlington, RM [1 ]
Baldwin, JE [1 ]
Lee, MH [1 ]
MacKinnon, CH [1 ]
机构
[1] OXFORD CTR MOL SCI, OXFORD OX1 3QY, ENGLAND
基金
英国工程与自然科学研究理事会;
关键词
D O I
10.1016/S0040-4020(97)00398-0
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The isolation and purification of alpha-ketoisocaproate dioxygenase [alpha-KICD] from rat liver is described. Sequence determination of the purified protein revealed it to have complete homology to rat liver 4-hydroxyphenylpyruvate dioxygenase [4-HPPD] which was confirmed by the cloning and expression of the gene encoding 4-HPPD in E. coli. Examination of the substrate specificity of the resulting soluble recombinant protein revealed it to be capable of the oxidative decarboxylation of a range of ketoacids derived from proteinogenic amino acids. The significance of the turnover of these different ketoacids is discussed in relation to the mechanism of this fascinating enzyme. (C) 1997 Elsevier Science Ltd.
引用
收藏
页码:6993 / 7010
页数:18
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