生命的神奇-过氧化氢酶保护我们免受危险的反应性氧化分子（ROS)

Catalase-Catalase protects us from dangerous reactive oxidizing molecules

 

上图：过氧化氢酶，红色的血红素和绿色的中央铁

与氧气共存是危险的。我们依靠氧气为我们的细胞供电，但氧气是一种反应性分子，如果不加以严格控制，可能会导致严重问题。氧气的一个危险是它很容易转化为其他活性化合物。在我们的细胞内，电子通过载体分子（例如来自核黄素和烟酸的载体）从一个位点连续穿梭到另一个位置。如果氧气进入这些载体分子之一，则电子可能会意外地转移到其中。这会将氧转化为危险的化合物，如超氧自由基（superoxide)和过氧化氢(H2O2)，可以攻击蛋白质中微妙的硫原子和金属离子。更糟糕的是，细胞中的游离铁离子偶尔会将过氧化氢转化为羟基自由基。这些致命的分子攻击并突变DNA。一个仍然存在争议的理论是，这种氧化损伤在我们生命的这些年里积累，导致我们衰老。

抗氧化剂的救援

 

幸运的是，细胞可以制造各种抗氧化酶，以对抗氧气对生命的危险副作用。两个重要的参与者是超氧化物歧化酶(SOD)，其将超氧化物自由基转化为过氧化氢(H2O2)，和过氧化氢酶(Catalase)，其将过氧化氢转化为水(H2O)和氧气(O2)。这些酶的重要性通过它们的g广泛存在来证明，其范围从大肠杆菌细胞中约0.1％的蛋白质到易感细胞类型中蛋白质的四分之一以上。这些过氧化氢酶分子在细胞内巡逻，抵消了过氧化氢的稳定产生并使其保持在安全水平。

 

更好，更强，更快

 

过氧化氢酶（Catalase)是细胞中发现的最有效的酶之一。每个过氧化氢酶分子每秒钟可分解数百万个过氧化氢分子。这里显示的牛过氧化氢酶（PDB条目8cat）和我们自己的过氧化氢酶使用铁离子来协助这种快速反应。该酶由四个相同的亚基组成，每个亚基都有自己的活性位点深埋在内部。以绿色显示的铁离子被夹在盘状血红素(heme)组的中心。过氧化氢酶，因为它们必须对抗活性分子，它们也是非常稳定的酶。注意四条链是如何交织在一起的，将整个复合体锁定在合适的形状中。

 

各种过氧化氢酶

上图：过氧化氢酶多样性：人红细胞过氧化氢酶（左），细菌HPII（中心）和细菌锰过氧化氢酶（右）。

　

不同的细胞构建不同类型的过氧化氢酶。许多可用于PDB的学习。从PDB条目1qqw左侧显示的保护我们红细胞的过氧化氢酶由四个相同的亚基组成，并使用血红素heme/铁(iron)基团进行反应。许多细菌用更大的过氧化氢酶清除过氧化氢，在PDB入口1iph的中心显示，使用类似的铁和血红素排列。其他细菌用完全不同的过氧化氢酶保护自己，过氧化氢酶使用锰离子而不是血红素，如PDB条目1jku右侧所示。有关基因组学角度的过氧化氢酶的更多信息，请查看欧洲生物信息学研究所的月度蛋白质。

 

过氧化氢酶分两步快速破坏过氧化氢。首先，过氧化氢分子结合并分裂。一个氧原子被提取并附着在铁原子上，其余的被释放为无害的水。然后，第二个过氧化氢分子结合。它也被分开并且碎片与铁结合的氧原子结合，释放水和氧气。 PDB进入2cag在这两步反应的中间捕获了过氧化氢酶。氧原子与铁结合，准备第二个过氧化氢分子结合。这里显示的组氨酸和天冬酰胺氨基酸有助于反应。单击图像以在交互式JSmol中探索此结构。

　

Catalase

Catalase protects us from dangerous reactive oxidizing molecules

 

Catalase, with the heme in red and the central iron in green.

Living with oxygen is dangerous. We rely on oxygen to power our cells, but oxygen is a reactive molecule that can cause serious problems if not carefully controlled. One of the dangers of oxygen is that it is easily converted into other reactive compounds. Inside our cells, electrons are continually shuttled from site to site by carrier molecules, such as carriers derived from riboflavin and niacin. If oxygen runs into one of these carrier molecules, the electron may be accidentally transferred to it. This converts oxygen into dangerous compounds such as superoxide radicals and hydrogen peroxide, which can attack the delicate sulfur atoms and metal ions in proteins. To make things even worse, free iron ions in the cell occasionally convert hydrogen peroxide into hydroxyl radicals. These deadly molecules attack and mutate DNA. One theory, still controversial, is that this type of oxidative damage accumulates over the years of our life, causing us to age.

Antioxidants to the Rescue

 

Fortunately, cells make a variety of antioxidant enzymes to fight the dangerous side-effects of life with oxygen. Two important players are superoxide dismutase, which converts superoxide radicals into hydrogen peroxide, and catalase, which converts hydrogen peroxide into water and oxygen gas. The importance of these enzymes is demonstrated by their prevalence, ranging from about 0.1% of the protein in an Escherichia coli cell to upwards of a quarter of the protein in susceptible cell types. These many catalase molecules patrol the cell, counteracting the steady production of hydrogen peroxide and keeping it at a safe level.

Better, Stronger, Faster

 

Catalases are some of the most efficient enzymes found in cells. Each catalase molecule can decompose millions of hydrogen peroxide molecules every second. The cow catalase shown here (PDB entry 8cat ) and our own catalases use an iron ion to assist in this speedy reaction. The enzyme is composed of four identical subunits, each with its own active site buried deep inside. The iron ion, shown in green, is gripped at the center of a disk-shaped heme group. Catalases, since they must fight against reactive molecules, are also unusually stable enzymes. Notice how the four chains interweave, locking the entire complex into the proper shape.

 

Kinds of Catalase

 

Different cells build different types of catalase. Many are available for study in the PDB. The catalase that protects our red blood cells, shown on the left from PDB entry 1qqw , is composed of four identical subunits and uses a heme/iron group to perform the reaction. Many bacteria scavenge hydrogen peroxide with a larger catalase, shown in the center from PDB entry 1iph , that uses a similar arrangement of iron and heme. Other bacteria protect themselves with an entirely different catalase that uses manganese ions instead of heme, as shown at the right from PDB entry 1jku . For more information on catalases from a genomic perspective, take a look at the Protein of the Month at the European Bioinformatics Institute.

 

Catalase performs its rapid destruction of hydrogen peroxide in two steps. First, a molecule of hydrogen peroxide binds and is broken apart. One oxygen atom is extracted and attached to the iron atom, and the rest is released as harmless water. Then, a second hydrogen peroxide molecule binds. It is also broken apart and the pieces are combined with the iron-bound oxygen atom, releasing water and oxygen gas. PDB entry 2cag  has captured catalase in the middle of this two-step reaction. The oxygen atom is bound to the iron, ready for the second hydrogen peroxide molecule to bind. The histidine and asparagine amino acids shown here assist with the reaction. Click on the image to explore this structure in an interactive JSmol.

 

http://pdb101.rcsb.org/motm/57