Formation of Unstable and very Reactive Chemical Species Catalyzed by Metalloenzymes: A Mechanistic Overview

Abstract

Nature has tailored a wide range of metalloenzymes that play a vast array of functions in all living organisms and from which their survival and evolution depends on. These enzymes catalyze some of the most important biological processes in nature, such as photosynthesis, respiration, water oxidation, molecular oxygen reduction, and nitrogen fixation. They are also among the most proficient catalysts in terms of their activity, selectivity, and ability to operate at mild conditions of temperature, pH, and pressure. In the absence of these enzymes, these reactions would proceed very slowly, if at all, suggesting that these enzymes made the way for the emergence of life as we know today. In this review, the structure and catalytic mechanism of a selection of diverse metalloenzymes that are involved in the production of highly reactive and unstable species, such as hydroxide anions, hydrides, radical species, and superoxide molecules are analyzed. The formation of such reaction intermediates is very difficult to occur under biological conditions and only a rationalized selection of a particular metal ion, coordinated to a very specific group of ligands, and immersed in specific proteins allows these reactions to proceed. Interestingly, different metal coordination spheres can be used to produce the same reactive and unstable species, although through a different chemistry. A selection of hand-picked examples of different metalloenzymes illustrating this diversity is provided and the participation of different metal ions in similar reactions (but involving different mechanism) is discussed.

Keywords: catalytic mechanism; iron; metalloenzymes; molybdenum; transition metals; zinc.

Scheme 1

General description of the catalytic mechanism of α-Carbonic anhydrase (CA). Only the atoms involved in the first coordination shell of the metal ion were included to simplify the representation.

Scheme 2

General description of the catalytic mechanism of Histone Deacetylase 8 (HDAC8). Only the atoms involved in the first coordination shell of the metal ion were represented to simplify the representation.

Scheme 3

General description of the catalytic mechanism of prolidase. Only the atoms involved in the first coordination shell of the metal ion were represented to simplify the representation.

Scheme 4

General description of the catalytic mechanism of urease. Only the atoms involved in the first coordination shell of the metal ion were represented to simplify the representation.

Scheme 5

General description of the catalytic mechanism of leucine aminopeptidase (LeuAP). Regarding amino acid residues belonging to the protein, only the atoms involved in the coordination of the metal were represented to simplify the representation.

Scheme 6

General description of the catalytic mechanism of xanthine oxidase (XO). Regarding amino acid residues belonging to the protein, only the atoms involved in the coordination of the metal were represented to simplify the representation.

Scheme 7

General description of the catalytic mechanism of formate dehydrogenase (FdH). Regarding amino acid residues belonging to the protein, only the atoms involved in the coordination of the metal were represented to simplify the representation.

Scheme 8

General description of the catalytic mechanism of alcohol dehydrogenases (ADH). Regarding amino acid residues belonging to the protein, only the atoms involved in the coordination of the metal were represented to simplify the representation.

Scheme 9

Schematic representation of the catalytic mechanism of ribonucleotide reductases (RNR) from class Ia (Fe–Fe). Regarding amino acid residues belonging to the protein, only the atoms involved in the coordination of the metal were represented to simplify the representation.

Scheme 10

Schematic representation of the catalytic mechanism of RNR from class Ib (Mn–Mn). Regarding amino acid residues belonging to the protein, only the atoms involved in the coordination of the metal were represented to simplify the representation.

Scheme 11

Schematic representation of the catalytic mechanism of methionine synthase (MetH). Regarding amino acid residues belonging to the protein, only the atoms involved in the coordination of the metal were represented to simplify the representation.

Scheme 12

General description of the catalytic mechanism of dopamine β-hydroxylase (DBH). Regarding amino acid residues belonging to the protein, only the atoms involved in the coordination of the metal were represented to simplify the representation.

Scheme 13

General description of the catalytic mechanism of myo-inosnitol oxygenase (MIOX). Regarding amino acid residues belonging to the protein, only the atoms involved in the coordination of the metal were represented to simplify the representation.