Department of Chemistry, Henry Wellcome Building, University of Leicester, Leicester LE1, UK.
FEBS J. 2012 Dec;279(24):4501-9. doi: 10.1111/febs.12036. Epub 2012 Nov 22.
Indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase catalyze the O(2) -dependent oxidation of l-tryptophan to N-formylkynurenine. Both are heme-containing enzymes, with a proximal histidine ligand, as found in the globins and peroxidases. From the structural information available so far, the distal heme pockets of these enzymes can contain a histidine residue (in tryptophan 2,3-dioxygenases), an arginine residue and numerous hydrophobic residues that line the pocket. We have examined the functional role of each of these residues in both human indoleamine 2,3-dioxygenase and human tryptophan 2,3-dioxygenase. We found that the distal histidine does not play an essential catalytic role, although substrate binding can be affected by removing the distal arginine and reducing the hydrophobic nature of the binding pocket. We collate the information obtained in the present study with that reported in the available literature to draw comparisons across the family and to provide a more coherent picture of how the heme pocket is optimized for tryptophan binding.
吲哚胺 2,3-双加氧酶和色氨酸 2,3-双加氧酶催化 l-色氨酸在 O(2)依赖性氧化作用下生成 N-甲酰犬尿氨酸。两者都是含有血红素的酶，具有近侧组氨酸配体，如球蛋白和过氧化物酶中发现的配体。根据目前已有的结构信息，这些酶的远端血红素口袋可以包含一个组氨酸残基（在色氨酸 2,3-双加氧酶中）、一个精氨酸残基和许多排列在口袋中的疏水性残基。我们已经研究了这两种酶中的每一种残基的功能作用。我们发现，远端组氨酸在催化中不起关键作用，尽管去除远端精氨酸和降低结合口袋的疏水性会影响底物结合。我们将本研究中获得的信息与现有文献中的报道进行了整理，对整个家族进行了比较，并提供了一个更连贯的画面，说明血红素口袋如何针对色氨酸结合进行了优化。
