Enzyme mimic (or

Artificial enzyme ''See also artificial metalloenzyme.'' An artificial enzyme is a synthetic organic molecule or ion that recreates one or more functions of an enzyme. It seeks to deliver catalysis at rates and selectivity observed in naturally occurring enzymes. ...

) is a branch of biomimetic chemistry, which aims at imitating the function of natural enzymes. An enzyme mimic is a

small molecule In molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs are small molecules; ...

complex that models the molecular structure, spectroscopic properties, or reactivity of an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

, sometimes called bioinspired complexes.Stephen J. Lippard, Jeremy M. Berg, ''Principles of Bioinorganic Chemistry'', University Science Books, 1994,

Overview

Enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

are biological catalysts: biopolymers that

catalyze Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

reaction Reaction may refer to a process or to a response to an action, event, or exposure. Physics and chemistry *Chemical reaction *Nuclear reaction *Reaction (physics), as defined by Newton's third law * Chain reaction (disambiguation) Biology and ...

. Although a small number of natural enzymes are built from

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

–termed

Ribozymes Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demons ...

–most enzymes are

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...

. Like any other protein, an enzyme is an

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

polymer A polymer () is a chemical substance, substance or material that consists of very large molecules, or macromolecules, that are constituted by many repeat unit, repeating subunits derived from one or more species of monomers. Due to their br ...

with added

cofactors Cofactor may also refer to: * Cofactor (biochemistry), a substance that needs to be present in addition to an enzyme for a certain reaction to be catalysed * A domain parameter in elliptic curve cryptography, defined as the ratio between the order ...

and other

post-translational modifications In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translation (biolog ...

. Often, most of the amino acid polymer is indirectly involved with the enzymes function, perhaps providing ancillary structure or connectivity, indirect activity regulation, or molecular identification of the enzyme. As a result, most enzymes are large molecules weighing many

kilodalton The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...

s. This bulk can obscure various investigative techniques such as

NMR Nuclear magnetic resonance (NMR) is a physical phenomenon in which atomic nucleus, nuclei in a strong constant magnetic field are disturbed by a weak oscillating magnetic field (in the near and far field, near field) and respond by producing ...

, EPR,

electrochemistry Electrochemistry is the branch of physical chemistry concerned with the relationship between Electric potential, electrical potential difference and identifiable chemical change. These reactions involve Electron, electrons moving via an electronic ...

crystallography Crystallography is the branch of science devoted to the study of molecular and crystalline structure and properties. The word ''crystallography'' is derived from the Ancient Greek word (; "clear ice, rock-crystal"), and (; "to write"). In J ...

, among others. It is standard practice to compare spectroscopic data from enzymes to similar spectroscopic data derived from better characterized small molecules. In this way, the understanding of metalloenzymes and other

metalloprotein Metalloprotein is a generic term for a protein that contains a metal ion cofactor. A large proportion of all proteins are part of this category. For instance, at least 1000 human proteins (out of ~20,000) contain zinc-binding protein domains al ...

s have developed. In many cases, the small molecule analogs were created for other reasons; however, it has been increasingly common for groups to intentionally make small molecule analogs also known as enzyme mimics. These enzyme mimics are prime examples of

bioinorganic chemistry Bioinorganic chemistry is a field that examines the role of metals in biology. Bioinorganic chemistry includes the study of both natural phenomena such as the behavior of metalloproteins as well as artificially introduced metals, including those t ...

Motivation

Most enzyme mimic studies are motivated by a combination of factors, including factors that are unrelated to the enzyme. Several of the factors that are related to the enzyme are listed below. Defining the active site structure. A number of important active sites are still poorly defined. This includes the

oxygen evolving complex The oxygen-evolving complex (OEC), also known as the water-splitting complex, is a water-oxidizing enzyme involved in the photo-oxidation of water during the light reactions of photosynthesis. OEC is surrounded by 4 core proteins of photosystem ...

and

nitrogenase Nitrogenases are enzymes () that are produced by certain bacteria, such as cyanobacteria (blue-green bacteria) and rhizobacteria. These enzymes are responsible for the reduction of nitrogen (N2) to ammonia (NH3). Nitrogenases are the only fa ...

. In an effort to understand these enzymes, small molecule analogs are created and compared to the data which exists for the proteins. Understanding the active site function. The structure of some enzymes are very well characterized, however, the function of some component of the active site is poorly understood. This is often investigated through

site-directed mutagenesis Site-directed mutagenesis is a molecular biology method that is used to make specific and intentional mutating changes to the DNA sequence of a gene and any gene products. Also called site-specific mutagenesis or oligonucleotide-directed mutagenes ...

. In addition, the synthesis of a model complex can suggest the function of various components. Reproducing the enzymes function. A number of enzymes are an interest since they catalyze a reaction chemist find challenging. These reactions include the partial oxidation of a hydrocarbon by

methane monooxygenase Methane monooxygenase (MMO) is an enzyme capable of oxidizing the C-H bond in methane as well as other alkanes. Methane monooxygenase belongs to the class of oxidoreductase enzymes (). There are two forms of MMO: the well-studied soluble form (s ...

(MMO) or the oxidation and production of

hydrogen Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...

hydrogenase A hydrogenase is an enzyme that Catalysis, catalyses the reversible Redox, oxidation of molecular hydrogen (H2), as shown below: Hydrogen oxidation () is coupled to the reduction of electron acceptors such as oxygen, nitrate, Ferric, ferric i ...

. "Functional" enzyme mimics or bioinspired catalysts are designed with characteristics of the enzyme in hopes of reproducing the enzymes functionality.

Significant examples

This list is extremely abbreviated in terms of the enzymes mimicked and the primary investigators working on each enzyme mimic. Richard Holm's work on mimics of

and creation of

iron sulfur cluster Iron is a chemical element; it has symbol Fe () and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, forming much of Earth's out ...

s. Stephen Lippard's work on MMO. Thomas Rauchfuss's, Marcetta Darensbourg's and Christopher Pickett's work on Hydrogenase mimics. Harry Gray's work with

porphyrin Porphyrins ( ) are heterocyclic, macrocyclic, organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (). In vertebrates, an essential member of the porphyrin group is heme, w ...

s complexes.

Ronald Breslow Ronald Charles David Breslow (March 14, 1931 – October 25, 2017) was an American chemist from Rahway, New Jersey. He was University Professor at Columbia University, where he was based in the Department of Chemistry and affiliated with the Depa ...

and Larry E. Overman coined the term of "artificial enzyme".

References

{{reflist Biochemistry Inorganic chemistry