Abstract
Organisms from all kingdoms of life use iron-proteins in a multitude of functional processes. We applied a bioinformatics approach to investigate the human portfolio of iron-proteins. We separated iron-proteins based on the chemical nature of their metal-containing cofactors: individual iron ions, heme cofactors and iron-sulfur clusters. We found that about 2% of human genes encode an iron-protein. Of these, 35% are proteins binding individual iron ions, 48% are heme-binding proteins and 17% are iron-sulfur proteins. More than half of the human iron-proteins have a catalytic function. Indeed, we predict that 6.5% of all human enzymes are iron-dependent. This percentage is quite different for the various enzyme classes. Human oxidoreductases feature the largest fraction of iron-dependent family members (about 37%). The distribution of iron proteins in the various cellular compartments is uneven. In particular, the mitochondrion and the endoplasmic reticulum are enriched in iron-proteins with respect to the average content of the cell. Finally, we observed that genes encoding iron-proteins are more frequently associated to pathologies than the all other human genes on average. The present research provides an extensive overview of iron usage by the human proteome, and highlights several specific features of the physiological role of iron ions in human cells.
Highlights
During evolution, organisms have selected some of the available elements from the environment to catalyze physiological reactions
Most of the iron ions in heme cofactors have only one ligand provided by the protein, which allows the substrate to occupy the second heme axial position
It is evident that there is a trend for human iron-proteins to have a lower number of residues in their iron-binding pattern (IBP) when the metal-binding site performs a catalytic function, in order to allow the iron ion to coordinate directly to the substrate as already observed for other metal containing proteins.[18]
Summary
Organisms have selected some of the available elements from the environment to catalyze physiological reactions. Some metal ions became essential to life. Iron is one of the most ancient and abundant transition metal ions in living organisms,[1,2] as it was highly available as ferrous ion in the early days of terrestrial life.[3] Iron is essential to all forms of life and participates in fundamental biological processes, such as photosynthesis, respiration and nitrogen fixation.[4,5] In cells, it is normally found in the +2 (ferrous) Paper. Metallomics or nitrogen atoms of cysteine and histidine side chains, respectively.[9] The metal site of rubredoxin, which contains a single iron ion coordinated by four cysteines, is generally classified as the simplest unit of iron–sulfur clusters. They are involved in a plethora of functional processes, including aerobic as well as anaerobic respiration, regulation of gene expression, amino acid and nucleotide metabolism, DNA modification and repair and tRNA modification
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