The mononuclear molybdenum enzymes.
The mononuclear molybdenum enzymes.
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DOI：
10.1021/cr400443z
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发表时间：
2014-04-09
期刊：
影响因子：
62.1
通讯作者：
Basu, Partha
中科院分区：
文献类型：
--
作者：
Hille, Russ;Hall, James;Basu, Partha
钼是大多数生物体所需的唯一第二行过渡金属，在生物学中几乎普遍分布。活性位点含钼的酶早已被发现，(1)目前已有50多种含钼酶被纯化并进行了生化表征；在基因组学和生物信息学分析的基础上，更多的基因产物被注释为假定的含钼蛋白。(2)在某些情况下，我们对酶的结构和功能之间的关系的理解是这样的，我们可以自信地谈论反应机制的详细性质，并且随着高分辨率x射线晶体结构的可用性，在活性位点的友好范围内稳定过渡态和加速反应速率的具体方法。与此同时，我们对伴随钼的有机辅因子（也被称为钼钼素或pyranopterin）的生物合成的理解，以及钼被纳入其中的方式，然后在插入载脂蛋白之前根据需要进行进一步修饰的方式也（至少在某些情况下）变得越来越好。现在已经确定，除氮酶（其中钼被纳入活性位点的[MoFe 7 S 9]簇）外，所有含钼酶都属于三个相互排斥的大家族，如酶黄嘌呤氧化酶，亚硫酸盐氧化酶和DMSO还原酶；这些酶是本报告的重点。(3)三个典型钼中心氧化Mo （VI）态的结构如图1所示，pyranopterin辅因子的结构也如图1所示。黄嘌呤氧化酶家族成员的活性位点具有方形配位几何的LMo VI OS （OH）结构。顶端配体是Mo= O配体，赤道面有两个来自蝶呤辅因子的烯二硫酸侧链的硫，一个催化不稳定的Mo - oh基团，最常见的是Mo= S。在这些酶的非功能形式中，赤道的Mo= S被第二个Mo= O取代；至少有一个元素的Mo= S被Mo= Se取代，其他元素的Mo= S被更复杂的- S - cu - S - cys取代，形成双核中心。亚硫酸盐氧化酶家族的成员有一个相关的LMo VI O 2 （S - cys）活性位点，同样是方形锥体，在赤道面上有一个顶端Mo= O和一个双齿烯二硫酸配体(L)，但在赤道面上有第二个Mo= O（而不是Mo - oh）和一个由蛋白质贡献的半胱氨酸配体（而不是Mo= S）完成钼配位球。最后一个家族是结构最多样化的，尽管所有成员都具有两个（而不仅仅是一个）等量的pyranopterin辅因子，并且具有l2 Mo VI Y (X)三角棱柱配位几何。DMSO还原酶本身有一个催化不稳定的Mo= O作为Y和一个丝氨酸配体作为X完成氧化酶的金属配位球。其他家族成员用半胱氨酸（细菌Nap质周硝酸盐还原酶）、硒代半胱氨酸（甲酸脱氢酶H）、- OH（亚砷酸盐氧化酶）或天冬氨酸（NarGHI异化硝酸盐还原酶）代替丝氨酸。有些酶用S甚至Se代替Mo= O基团。DMSO还原酶家族的成员与含钨酶的醛铁氧还蛋白氧化还原酶家族的成员具有普遍的结构同源性；(4)事实上，第一个被晶体学表征的含吡蝶呤酶是钨…
Molybdenum is the only second-row transition metal required by most living organisms, and is nearly universally distributed in biology. Enzymes containing molybdenum in their active sites have long been recognized,(1) and at present over 50 molybdenum-containing enzymes have been purified and biochemically characterized; a great many more gene products have been annotated as putative molybdenum-containing proteins on the basis of genomic and bioinformatic analysis.(2) In certain cases, our understanding of the relationship between enzyme structure and function is such that we can speak with confidence as to the detailed nature of the reaction mechanism and, with the availability of high-resolution X-ray crystal structures, the specific means by which transition states are stabilized and reaction rate is accelerated within the friendly confines of the active site. At the same time, our understanding of the biosynthesis of the organic cofactor that accompanies molybdenum (variously called molybdopterin or pyranopterin), the manner in which molybdenum is incorporated into it, and then further modified as necessary prior to insertion into apoprotein has also (in at least some cases) become increasingly well understood.It is now well-established that all molybdenum-containing enzymes other than nitrogenase (in which molybdenum is incorporated into a [MoFe 7 S 9] cluster of the active site) fall into three large and mutually exclusive families, as exemplified by the enzymes xanthine oxidase, sulfite oxidase, and DMSO reductase; these enzymes represent the focus of the present account.(3) The structures of the three canonical molybdenum centers in their oxidized Mo (VI) states are shown in Figure 1, along with that for the pyranopterin cofactor. The active sites of members of the xanthine oxidase family have an LMo VI OS (OH) structure with a square-pyramidal coordination geometry. The apical ligand is a Mo= O ligand, and the equatorial plane has two sulfurs from the enedithiolate side chain of the pyranopterin cofactor, a catalytically labile Mo–OH group, and most frequently a Mo= S. Nonfunctional forms of these enzymes exist in which the equatorial Mo= S is replaced with a second Mo= O; in at least one member of the family the Mo= S is replaced by a Mo= Se, and in others it is replaced by a more complex− S–Cu–S–Cys to give a binuclear center. Members of the sulfite oxidase family have a related LMo VI O 2 (S–Cys) active site, again square-pyramidal with an apical Mo= O and a bidentate enedithiolate Ligand (L) in the equatorial plane but with a second equatorial Mo= O (rather than Mo–OH) and a cysteine ligand contributed by the protein (rather than a Mo= S) completing the molybdenum coordination sphere. The final family is the most diverse structurally, although all members possess two (rather than just one) equiv of the pyranopterin cofactor and have an L 2 Mo VI Y (X) trigonal prismatic coordination geometry. DMSO reductase itself has a catalytically labile Mo= O as Y and a serinate ligand as X completing the metal coordination sphere of oxidized enzyme. Other family members have cysteine (the bacterial Nap periplasmic nitrate reductases), selenocysteine (formate dehydrogenase H),− OH (arsenite oxidase), or aspartate (the NarGHI dissimilatory nitrate reductases) in place of the serine. Some enzymes have S or even Se in place of the Mo= O group. Members of the DMSO reductase family exhibit a general structural homology to members of the aldehyde: ferredoxin oxidoreductase family of tungsten-containing enzymes;(4) indeed, the first pyranopterin-containing enzyme to be crystallographically characterized was the tungsten …
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影响因子：
2.9
作者：
Anderson, LJ;Richardson, DJ;Butt, JN
通讯作者：
Butt, JN
影响因子：
3.2
作者：
Afshar, S;Johnson, E;Schröder, I
通讯作者：
Schröder, I
影响因子：
3.9
作者：
Alfaro, Joshua F.;Joswig-Jones, Carolyn A.;Jones, Jeffrey P.
通讯作者：
Jones, Jeffrey P.
影响因子：
3.2
作者：
Anderson, LA;McNairn, E;Boxer, DH
通讯作者：
Boxer, DH
DOI：
10.1038/nsb994
发表时间：
2003-11-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Arnoux, P;Sabaty, M;Pignol, D
通讯作者：
Pignol, D