Focus on molecules: ALDH1A1: from lens and corneal crystallin to stem cell marker.
Focus on molecules: ALDH1A1: from lens and corneal crystallin to stem cell marker.
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DOI：
10.1016/j.exer.2011.04.008
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发表时间：
2012-09
影响因子：
3.4
通讯作者：
Vasiliou, Vasilis
中科院分区：
文献类型：
--
作者：
Chen, Ying;Koppaka, Vindhya;Thompson, David C.;Vasiliou, Vasilis
醛脱氢酶1A1 （ALDH1A1）属于一个超家族的酶，其中大部分催化各种内源性和外源性醛底物的NAD (P)+依赖性不可逆氧化成相应的酸（Marchitti et al., 2008）。ALDH1A1在物种间具有良好的保守性，其氨基酸序列与哺乳动物的同源性为90%，与其他物种（包括鸡、蛙和鱼）的同源性为80%。在所有这些物种中，NAD+结合必需的残基（Lys-192、Gly-245、Gly-250、Glu-399和Phe-401；编号基于人类ALDH1A1）和催化活性必需的残基（Cys-302和Glu-268）都是严格保守的。在结构上，哺乳动物ALDH1A1是一个具有55 kDa亚基的四聚体。每个单体（图1A）由一个βαβ n端核苷酸结合结构域（黄色）、一个βαβ催化结构域（蓝色）和一个c端小β片寡聚化结构域（粉红色）组成。二聚体是通过单体α-螺旋的接触和β-片的延伸在催化域和寡聚域之间形成的。在四聚体全酶中（图1B），活性位点位于从酶表面穿出的疏水通道的底部，靠近四聚体界面，与辅因子结合位点相对，有利于催化。有趣的是，线圈程序(http://www。ch. embnet。org/software/COILS_form。html)预测了人类ALDH1A1蛋白序列中位于81-99、114-144和172-183个残基的三个螺旋结构基（图1A，橙色），它们位于核苷酸结合结构域。螺旋结构域是一个高度稳定的寡聚化基序，存在于多种蛋白质中，在基因调控、细胞通讯、膜融合和药物挤出等方面发挥作用。
Aldehyde dehydrogenase 1A1 (ALDH1A1) belongs to a superfamily of enzymes, most of which catalyze the NAD (P)+-dependent irreversible oxidation of a wide variety of endogenous and exogenous aldehyde substrates to their corresponding acids (Marchitti et al., 2008). ALDH1A1 is well conserved across species, showing 90% identity in amino acid sequence with mammals and 80% with other species, including chicken, frog and fish. In all of these species, the essential residues for NAD+-binding (Lys-192, Gly-245, Gly-250, Glu-399 and Phe-401; numbering based on human ALDH1A1) and for catalytic activity (Cys-302 and Glu-268) are strictly conserved. Structurally, mammalian ALDH1A1 is a homotetramer with a 55 kDa subunit. Each monomer (Fig. 1A) is composed of an βαβ N-terminal nucleotide-binding-domain (yellow), a βαβ catalytic domain (blue) and a C-terminal small β-sheet oligomerization domain (pink). The dimer is formed through the contacts of monomer α-helices and β-sheet extension between the catalytic and oligomerization domains. In the tetrameric holoenzyme (Fig. 1B), the active sites reside at the base of a hydrophobic tunnel penetrating from the surface of the enzyme and they are close to the tetrameric interface and opposite to the cofactor binding sites, which is beneficial to catalysis. Interestingly, the COILS program (http://www. ch. embnet. org/software/COILS_form. html) predicts three coiled-coil motifs in human ALDH1A1 protein sequence at 81–99, 114–144, and 172–183 residues (Fig. 1A, orange), which reside in the nucleotide-binding-domain. The coiled-coil domain is a highly stable oligomerization motif found in diverse proteins functioning in gene regulation, cell communication, membrane fusion and drug extrusion.
影响因子：
4.8
作者：
Lassen, Natalie;Bateman, J. Bronwyn;Vasiliou, Vasilis
通讯作者：
Vasiliou, Vasilis