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Peters, John W.

Dr. John W. Peters

Associate Professor
Department of Chemistry and Biochemistry
Montana State University
Bozeman, MT
Our primary interests are structure/function relationships in metal-containing proteins.  X-ray diffraction techniques are used to determine the three-dimensional structure of proteins.  The structures serve as a basis for understanding the molecular mechanisms of enzyme-catalyzed reactions.  Our current areas of active research are hydrogen metabolism, nitrogen metabolism, biodegradation of aliphatic ketones and epoxides, and therapeutic phosphatase inhibition.  A synopsis for each of these projects is described below.


The reversible conversion of molecular hydrogen (H2) to protons and electrons is a central reaction in the global biological energy cycle.  Hydrogenase enzymes catalyze a large percentage of this reaction, and thus a more detailed understanding of these enzymes is of wide interest in biotechnology, biochemistry, and energy sciences. These enzymes are present in various microorganisms and function either in the utilization of H2 as a growth substrate (H2 uptake) or in certain anaerobic bacteria to dispose of excess electrons by combining them with protons to form H2 (H2 evolution).  Recently, the X-ray crystal structure of the iron-only hydrogenase from the anaerobic soil microorganism Clostridium pasteurianum (CpI) was determined to 1.8 Å resolution in the group. CpI is a highly complex protein containing 20 iron atoms arranged into 5 individual metal cluster assemblies.  The active site cluster or "H cluster" (left) is structurally unprecedented among previously characterized biological iron-sulfur clusters.  Our ongoing hydrogenase research involves the structural characterization of inhibited and poised redox states of CpI and the structural characterization of additional enzymes of this class.


Biological nitrogen fixation is a process by which microorganisms convert atmospheric nitrogen to ammonia.   The ammonia generated in this process is utilized by plants as a source of nitrogen for the synthesis of necessary proteins and nucleic acids.  Since the industrial production of fertilizers is highly costly and can produce environmentally unfriendly byproducts, research on biological nitrogen fixation is of agronomic, economic, and environmental importance.  In all known biological systems, nitrogen fixation is catalyzed by the enzyme nitrogenase.  In our research we are interested in the role of MgATP in nitrogenase catalysis.  MgATP contains energy in the form of high-energy bonds that drive the overall process and is a general mechanism used to drive numerous cellular processes including cell differentiation, DNA replication, and protein synthesis.  During nitrogenase catalysis, the binding and hydrolysis of MgATP confer conformationally distinct structural states on the nitrogenase complex that promote macromolecular complex formation and electron transfer reactions directed at the conversion of nitrogen to ammonia.  With the use of MgATP analogs and site-directed variants of the nitrogenase components we are able to trap various conformations of the enzyme and characterize them by X-ray diffraction methods.  This supplies us with various snapshots of the nitrogenase at work and from these snapshots we can better understand the fundamental mechanism of nitrogenase catalysis and the manner in which the MgATP binding and hydrolysis are harnessed to drive this fundamental process.  Recently the structure of the MgADP bound state of the nitrogenase Fe protein was determined in the group.


The modification of proteins by attaching or removing phosphate, which is termed protein phosphorylation, is now recognized as a mechanism widely used by plant and animal cells to regulate their functions.  The enzymes that accomplish these transformations play essential roles in the regulation of many cellular processes including growth, metabolism, and the immune response.  This project’s goal is to explore a new class of compounds, thiophosphonates, which can be adapted to selectively inhibit particular members of this family of enzymes.  This work has the potential to lead to the development of a novel class of therapeutic agents for the treatment of diabetes and leukemia, and of new immunosuppressants for the treatment of autoimmune diseases and organ transplant recipients.  Because a number of these enzymes are involved in bacterial pathogenicity, inhibitors of these enzymes also have the potential to lead to a novel class of antibiotics.  Because of the number and ubiquity of these important enzymes, this concept has the potential to lead to a whole new class of therapeutic compounds.

Enzymes Involved in the Degradation of Aliphatic Ketones and Epoxides

This project involves structural studies aimed at probing the chemical mechanisms of the enzymes responsible for the microbial metabolism of propylene and isopropanol in Xanthobacter strain Py2.   These convergent metabolic pathways produce epoxides during the metabolism of alkenes or ketones during the metabolism of isopropanol as intermediates.  These intermediates are converted to the central metabolite acetoacetate through novel biochemical reactions involving the fixation of carbon dioxide.  Large quantities of epoxides are synthesized industrially as sterilants or as a starting material for the synthesis of various polymeric resins.   Since these compounds are potent alkylating reagents and can give rise to covalent modification of DNA and proteins, they are a potential health hazard.  Acetone is a toxic molecule that is synthesized industrially and formed biologically during bacterial fermentation and mammalian starvation. As such, there is considerable interest in chemical transformations that allow conversion of these compounds to compounds that are not hazardous..