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首页> 外文期刊>Acta crystallographica. Section D, Structural biology. >Structural studies of substrate and product complexes of 5‐aminolaevulinic acid dehydratase from humans, Escherichia coli Escherichia coli and the hyperthermophile Pyrobaculum calidifontis Pyrobaculum calidifontis
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Structural studies of substrate and product complexes of 5‐aminolaevulinic acid dehydratase from humans, Escherichia coli Escherichia coli and the hyperthermophile Pyrobaculum calidifontis Pyrobaculum calidifontis

机译：底物和产品结构的研究配合物5 aminolaevulinic酸脱水酶从人类,大肠杆菌大肠杆菌和超嗜热菌Pyrobaculum calidifontis

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A number of X‐ray analyses of an enzyme involved in a key early stage of tetrapyrrole biosynthesis are reported. Two structures of human 5‐aminolaevulinate dehydratase (ALAD), native and recombinant, have been determined at 2.8?? resolution, showing that the enzyme adopts an octameric quaternary structure in accord with previously published analyses of the enzyme from a range of other species. However, this is in contrast to the finding that a disease‐related F12L mutant of the human enzyme uniquely forms hexamers [Breinig et al. (2003), Nature Struct. Biol. 10 , 757–763]. Monomers of all ALADs adopt the TIM‐barrel fold; the subunit conformation that assembles into the octamer includes the N‐terminal tail of one monomer curled around the (α/β) 8 barrel of a neighbouring monomer. Both crystal forms of the human enzyme possess two monomers per asymmetric unit, termed A and B . In the native enzyme there are a number of distinct structural differences between the A and B monomers, with the latter exhibiting greater disorder in a number of loop regions and in the active site. In contrast, the second monomer of the recombinant enzyme appears to be better defined and the active site of both monomers clearly possesses a zinc ion which is bound by three conserved cysteine residues. In native human ALAD, the A monomer also has a ligand resembling the substrate ALA which is covalently bound by a Schiff base to one of the active‐site lysines (Lys252) and is held in place by an ordered active‐site loop. In contrast, these features of the active‐site structure are disordered or absent in the B subunit of the native human enzyme. The octameric structure of the zinc‐dependent ALAD from the hyperthermophile Pyrobaculum calidifontis is also reported at a somewhat lower resolution of 3.5??. Finally, the details are presented of a high‐resolution structure of the Escherichia coli ALAD enzyme co‐crystallized with a noncovalently bound moiety of the product, porphobilinogen (PBG). This structure reveals that the pyrrole side‐chain amino group is datively bound to the active‐site zinc ion and that the PBG carboxylates interact with the enzyme via hydrogen bonds and salt bridges with invariant residues. A number of hydrogen‐bond interactions that were previously observed in the structure of yeast ALAD with a cyclic intermediate resembling the product PBG appear to be weaker in the new structure, suggesting that these interactions are only optimal in the transition state.
机译：大量的X射线分析涉及的一种酶在一个关键的早期阶段四吡咯生物合成报告。5列车aminolaevulinate脱水酶(ALAD),本地和重组,已经确定为2.8 ? ?分辨率,表明酶采用一个在符合octameric四级结构先前发表的分析的酶一系列的其他物种。对比发现疾病相关F12L酶突变的人类独特的形式五个一[Breinig et al。(2003),自然结构。医学杂志。757 - 763年)。蒂姆桶应承担的褶皱;组装成八聚物包括N量终端一个单体卷曲的尾巴(α/β)8桶一个邻近的单体。晶体形式的人类酶有两个单体/不对称单位,称为A和B。本机酶有很多不同A和B之间的结构差异单体,后者表现出更障碍的循环区域和数量活跃的站点。重组酶似乎更好定义和两个单体的活性部位显然具有锌离子所束缚三个守恒的半胱氨酸残基。人类ALAD,单体也有配体类似底物共价阿拉巴马州受一个席夫碱的一个活跃的站点赖氨酸(Lys252)和举行的命令活跃网站循环。活跃的特点的网站结构无序或B亚基的缺席本地人工酶。超嗜热菌的锌依赖ALAD应承担的Pyrobaculum calidifontis也在报道有些低分辨率3.5 ? ?。高分辨率的细节了大肠杆菌ALAD酶的结构公司结晶与共价的一部分产品的胆色素原(PBG)。结构表明,吡咯侧链氨基配绑定到活跃的网站锌离子,PBG羧化物交互通过氢键与酶和盐桥梁与不变的残留物。氢债券以前的交互观察在酵母ALAD的结构循环中间像百事装瓶集团的产品似乎较弱的新结构,这表明这些交互只最优的过渡状态。

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