Altered specificity mutations define residues essential for substrate positioning in xanthine dehydrogenase
Altered specificity mutations define residues essential for substrate positioning in xanthine dehydrogenase
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DOI：
10.1006/jmbi.1998.1707
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发表时间：
1998-05-01
影响因子：
5.6
通讯作者：
Scazzocchio, C
中科院分区：
文献类型：
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作者：
Glatigny, A;Hof, P;Scazzocchio, C
我们描述了构巢曲霉黄嘌呤脱氢酶（XDH）的一些突变的序列变化。我们已经找到了受这些变化影响的氨基酸的三维（3D）结构的醛氧化还原酶（MOP）从脱硫弧菌的巨大，有关真核XDH。其中，两个是功能缺失突变，分别定位于腺嘌呤-蝶呤辅因子（MoCo）结构域和底物识别相关结构域。两个氨基酸的变化导致对不可逆抑制剂别嘌呤醇的抗性。在Arg 911中，在所有XDH和MOP中保守但在其它醛氧化酶（AO）中不保守的两个不同的变化将类似物2-羟基嘌呤的羟基化位置从C-8改变为C-6。许多变化影响邻近钼或其配体的残基。Arg 911以这样的方式定位在底物口袋中，即它可以解释嘌呤底物相对于MoCo反应中心的定位，以及在XDH（Glu 833）中普遍保守的谷氨酸残基。(C)出版社：Academic Press Limited。
We describe the sequence changes of a number of mutations of the Aspergillus nidulans xanthine dehydrogenase (XDH). We have located the amino acids affected by these changes in the three-dimensional(3D) structure of aldehyde oxido-reductase (MOP) from Desulfovibrio gigas, related to eukaryotic XDHs. Of these, two are loss of function mutations, mapping, respectively, in the molybdenum-pterin co-factor (MoCo) domain and in the domain involved in substrate recognition. Changes in two amino acids result in resistance to the irreversible inhibitor allopurinol. in Arg911 two different changes, conserved among all XDHs and MOP but not in other aldehyde oxidases (AO), change the position of hydroxylation of the analogue 2-hydroxypurine from C-8 to C-6. A number of changes affect residues adjacent to the molybdenum or its ligands. Arg911 is positioned in the substrate pocket in a way that it can account for the positioning of purine substrates in relation to the MoCo reactive center, together with a glutamate residue, universally conserved among the XDHs (Glu833). (C) 1998 Academic Press Limited.