The Bioinformatics And Chemoinformatics Study In The Usage Bias Of Redox Cofactors

Oxidation-reduction reaction (also called redox reaction) is one of the most basic and important biochemical actions in organisms. But as amino acids do not have a good ability of receiving and losing electrons, so most oxidoreductases redox functions are undertaken by protein cofactors. A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. Cofactors can be divided into two broad groups:organic cofactors (e.g., nicotinamide-adenine-dinucleotide (NAD), nicotinamide-adenine-dinucleotide phosphate (NADP), flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD)) and metal ions (e.g., zinc, iron, manganese, nickel and cobalt). Because both kinds of redox cofactors have a good ability of receiving and losing electrons, so it is necessary to explore which kind of cofactors was more involved in the redox processes of oxidoreductases.In this article we used bioinformatics and chemoinformatics methods to analyze redox reactions in organisms. At first, we analyzed the usage of cofactors of all oxidoreductases (1151 EC numbers) by searching SWISS-PROT/TrEMBL database, and found that 76.1% of oxidoreductases used organic cofactors and 14.3% used metal ions. Secondly, in order to explore the usage bias of cofactors, we analyzed the cofactors usage in 41 species by bioinformatics method and found the distribution rule:about 90% redox enzymes used organic cofactors in archaeon and prokaryotes and about 78% redox enzymes used organic cofactors in eukaryotes. For explaining this rule, we had done the following researches:On the one hand, we analyzed the redox reaction equations. The results indicated that 28.5% organic enzymes reactions need oxygen and 63.2% metallic enzymes reactions need oxygen. Therefore, we inferred that the emergence of oxygen was one of the most important reasons probably that induced the increase the usage frequency of metallic cofactors. On the other hand, we analyzed the chemical characters of small molecules participating in the redox reactions. The results indicated that the small molecules of metallic reactions group were more hydrophobic. Therefore, we inferred that the usage of metallic cofactors were suitable for hydrophobic environment.