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Richard N. Armstrong

Title and Contact Information

Professor of Biochemistry & Chemistry
Office: 842 RRB
Phone: (615) 343-2920


Ph.D., Marquette University, 1975


Bioorganic Chemistry
Center for Structural Biology
Chemical Biology
Mechanistic Enzymology

In The News

ACS-Professor Armstrong receives: The Repligen Award in Chemistry of Biological Processes
Reporter-VU's Armstrong recognized by Karolinska Institute
ACS-Professor Armstrong named Fellow of the American Chemical Society



Structural And Mechanistic Enzymology

Research efforts in Professor Armstrong's laboratory are embodied in three projects directed at elucidating the mechanisms of action of enzymes involved in the metabolism of foreign or xenobiotic molecules. These catalysts, known as detoxication enzymes, are essential components of any organism's ability to resist chemical insult.

The first project is a study of glutathione transferases, a family of enzymes involved in the metabolism of electrophilic molecules such as expoxides, alkyl halides and a,b-unsaturated carbonyl compounds. From studies of the physical organic chemistry occurring in the active site, aspects of the kinetic, chemical, and stereochemical mechanisms of these enzymes have been elucidated. In addition, high-resolution three-dimensional structures of several glutathione transferases have been solved and are being used as a guide in the construction of chimeric or hybrid enzymes with altered catalytic properties. The functional properties of the mutant enzymes provide insight into the specific role of various amino acid residues in the region of the active site. The site-general and site-specific incorporation of unnatural amino acids into this enzyme is being investigated as a tool to refine our understanding of the mechanism of catalysis.

Many detoxication enzymes are membrane-bound and pose unique problems for mechanistic analysis. In a second project two membrane-bound detoxication enzymes, enzymes epoxide hydrolase and UDP-glucuronosyltransferase are being investigated. Efficient expression systems are being developed for these enzymes to facilitate structural and mechanistic studies. The discovery that epoxide hydrolase proceeds via a covalent ester intermediate has aided in the identification of active site residues that participate in catalysis and has helped define the evolutionary relationship of this protein with other hydrolase enzymes.

Microorganisms also have detoxication enzymes which allow them to use many organic compounds as energy sources or to resist the toxic effect of antibiotics. This later phenomenon contributes to the erosion of the efficacy of clinically useful antibiotics and represents a serious human health problem. The objectives of the third research project are to elucidate the catalytic mechanisms and structures of enzymes involved in the resistance of microorganisms to the antibiotic fosfomycin. These objectives include, (i) the construction of high-level expression systems for fosfomycin resistance proteins; (ii) elucidation of the catalytic mechanisms of the enzymes, by spectroscopic, steady state and pre-steady state kinetic techniques; and (iii) determination of the three-dimensional structures by X-ray crystallography. The information will provide a rational basis for the design of new drugs to counter antibiotic resistance.

Selected Publications

Thompson MK, Keithly ME, Goodman MC, Hammer ND, Cook PD, Jagessar KL, Harp J, Skaar EP, Armstrong RN. Structure and Function of the Genomically Encoded Fosfomycin Resistance Enzyme, FosB, from Staphylococcus aureus. Biochemistry. 2014, 53 (4): 755-765.

Morgan TM, Seeley EH, Fadare O, Caprioli RM, Clark PE. Imaging the Clear Cell Renal Cell Carcinoma Proteome. Journal of Urology. 2013, 189 (3): 1097-1103.

Yang JH, Caprioli RM. Matrix Precoated Targets for Direct Lipid Analysis and Imaging of Tissue. Analytical Chemistry. 2013, 85 (5): 2907-2912.

Thiery-Lavenant G, Zavalin AI, Caprioli RM. Targeted Multiplex Imaging Mass Spectrometry in Transmission Geometry for Subcellular Spatial Resolution. Journal of the American Society for Mass Spectrometry. 2013, 24 (4): 609-614.

Mike LA, Dutter BF, Stauff DL, Moore JL, Vitko NP, Aranmolate O, Kehl-Fie TE, Sullivan S, Reid PR, DuBois JL, Richardson AR, Caprioli RM, Sulikowski GA, Skaar EP. Activation of heme biosynthesis by a small molecule that is toxic to fermenting Staphylococcus aureus. Proceedings of the National Academy of Sciences of the United States of America. 2013, 110 (20): 8206-8211.

Angel PM, Caprioli RM. Matrix-Assisted Laser Desorption Ionization Imaging Mass Spectrometry: In Situ Molecular Mapping. Biochemistry. 2013, 52 (22): 3818-3828.

Preininger AM, Kaya AI, Gilbert JA, Busenlehner LS, Armstrong RN, Hamm HE. Myristoylation Exerts Direct and Allosteric Effects on G alpha Conformation and Dynamics in Solution. Pharmazeutische Industrie. 2012, 74 (2): 1911-1924.

Prage EB, Morgenstern R, Jakobsson PJ, Stec DF, Voehler MW, Armstrong RN. Observation of Two Modes of Inhibition of Human Microsomal Prostaglandin E Synthase 1 by the Cyclopentenone 15-Deoxy-Delta(12,14)-prostaglandin J(2). Biochemistry. 2012, 51 (11): 2348-2356.

Gerlt JA, Allen KN, Almo SC, Armstrong RN, Babbitt PC, Cronan JE, Dunaway-Mariano D, Imker HJ, Jacobson MP, Minor W, Poulter CD, Raushel FM, Sali A, Shoichet BK, Sweedler JV. The Enzyme Function Initiative. Biochemistry. 2011, 50 (46): 9950-9962.

Prage EB, Pawelzik SC, Busenlehner LS, Kim K, Morgenstern R, Jakobsson PJ, Armstrong RN. Structure Location of Inhibitor Binding Sites in the Human Inducible Prostaglandin E Synthase, MPGES1. Biochemistry. 2011, 50 (35): 7684-93.

Apweiler R, Armstrong R, Bairoch A, Cornish-Bowden A, Halling Stourman NV, Branch MC, Schaab MR, Harp JM, Ladner JE, Armstrong RN. Structure and Function of YghU, a Nu-Class Glutathione Transferase Related to YfcG from Escherichia coli. Biochemistry. 2011, 50 (7): 1274-81.

Apweiler R, Armstrong R, Bairoch A, Cornish-Bowden A, Halling PJ, Hofmeyr JHS, Kettner C, Leyh TS, Rohwer J, Schomburg D, Steinbeck C, Tipton K. A large-scale protein-function database. Nature Chemical Biology. 2010, 6 (11): 785-785.