Enzyme mimic

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Enzyme mimic (or Artificial enzyme ) is a branch of biomimetic chemistry, which aims at imitating the function of natural enzymes. [1] [2] [3] [4] [5] An enzyme mimic is a small molecule complex that models the molecular structure, spectroscopic properties, or reactivity of an enzyme, sometimes called bioinspired complexes. [6]

Contents

Overview

Enzymes are biological catalysts: biopolymers that catalyze a reaction. Although a small number of natural enzymes are built from RNA–termed Ribozymes–most enzymes are proteins. Like any other protein, an enzyme is an amino acid polymer with added cofactors and other post-translational modifications. 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 kilodaltons. This bulk can obscure various investigative techniques such as NMR, EPR, electrochemistry, crystallography, 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 metalloproteins 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.

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 and nitrogenase. 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. 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 (MMO) or the oxidation and production of hydrogen by hydrogenase. "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 nitrogenase and creation of iron sulfur clusters.

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 porphyrins complexes.

Ronald Breslow and Larry E. Overman coined the term of "artificial enzyme". [3]

Related Research Articles

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Nitrogenase

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Methane monooxygenase

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Ronald Breslow

Ronald Charles D. Breslow 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 Departments of Biological Sciences and Pharmacology; he had also been on the faculty of its Department of Chemical Engineering. He had taught at Columbia since 1956 and was a former chair of the university's chemistry department.

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Richard Hadley Holm, also known as R. H. Holm, is an American inorganic chemist.

Stephen J. Lippard

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Amy C. Rosenzweig is a professor of Chemistry and Molecular Biosciences at Northwestern University. She was born in 1967 in Pittsburgh, Pennsylvania. She received her BA in chemistry from Amherst College in 1988, and her Ph.D. from Massachusetts Institute of Technology in 1994. At MIT, Rosenzweig worked under the supervision of Stephen J. Lippard where she pioneered the structural studies of the hydroxylase component of methane monooxygenase from methyloccous capsulatus. Her current research interests include structural biology and bioinorganic chemistry, metal uptake and transport, oxygen activation by metalloenzymes, and characterization of membrane protein. For her work, she has been recognized by a number of national and international awards, including the MacArthur "Genius" Award in 2003.

Marcetta York Darensbourg is an American inorganic chemist. She is a Distinguished Professor of Chemistry at Texas A&M University. Her current work focuses on iron hydrogenases and iron nitrosyl complexes.

[NiFe] hydrogenase is a type of hydrogenase, which is an oxidative enzyme that reversibly convert molecular hydrogen in prokaryotes including Bacteria and Archaea. The catalytic site on the enzyme provides simple hydrogen-metabolizing microorganisms a redox mechanism by which to store and utilize energy via the reaction shown in Figure 1. This is particularly essential for the anaerobic, sulfate-reducing bacteria of the genus Desulfovibrio as well as pathogenic organisms Escherichia coli and Helicobacter pylori. The mechanisms, maturation, and function of [NiFe] hydrogenases are actively being researched for applications to the hydrogen economy and as potential antibiotic targets.

FeMoco Cofactor of nitrogenase

FeMoco (FeMo cofactor) is the primary cofactor of nitrogenase. Nitrogenase is the enzyme that catalyzes the conversion of atmospheric nitrogen molecules N2 into ammonia (NH3) through the process known as nitrogen fixation. Containing iron and molybdenum, the cofactor is called FeMoco. Its stoichiometry is Fe7MoS9C.

Wolfgang Lubitz

Wolfgang Lubitz is a German chemist and biophysicist. He is currently a director emeritus at the Max Planck Institute for Chemical Energy Conversion. He is well known for his work on bacterial photosynthetic reaction centres, hydrogenase enzymes, and the oxygen-evolving complex using a variety of biophysical techniques. He has been recognized by a Festschrift for his contributions to electron paramagnetic resonance (EPR) and its applications to chemical and biological systems.

Serena DeBeer is an American chemist. She is currently a W3-Professor and the director at the Max Planck Institute for Chemical Energy Conversion in Muelheim an der Ruhr, Germany, where she heads the Department of Inorganic Spectroscopy. Her expertise lies in the application and development of X-ray based spectroscopic methods as probes of electronic structure in biological and chemical catalysis.

References

  1. ↑ "Breslow Group Homepage". www.columbia.edu. Retrieved 2015-12-11.
  2. ↑ Breslow, Ronald (1995-03-01). "Biomimetic Chemistry and Artificial Enzymes: Catalysis by Design". Accounts of Chemical Research. 28 (3): 146–153. doi:10.1021/ar00051a008. ISSN   0001-4842.
  3. 1 2 Breslow, Ronald; Overman, Larry E. (1970-02-01). ""Artificial enzyme" combining a metal catalytic group and a hydrophobic binding cavity". Journal of the American Chemical Society. 92 (4): 1075–1077. doi:10.1021/ja00707a062. ISSN   0002-7863.
  4. ↑ "Wiley: Artificial Enzymes - Ronald Breslow". as.wiley.com. Retrieved 2015-12-11.
  5. ↑ Kirby, Anthony J; Hollfelder, Florian. "From Enzyme Models to Model Enzymes (RSC Publishing) Anthony J Kirby, Florian Hollfelder". pubs.rsc.org. Retrieved 2015-12-11.
  6. ↑ Stephen J. Lippard, Jeremy M. Berg, Principles of Bioinorganic Chemistry, University Science Books, 1994, ISBN   0-935702-72-5
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