Lesa J. Beamer, PhD



Contact Information

Email BeamerL@missouri.edu
Phone 573-882-6072
Address 105A Schlundt Annex


BS Chemistry Kent State University Kent, Ohio
PhD Biochemistry Johns Hopkins School of Medicine Baltimore, Md.

Research Area

Structural biology: X-ray crystallography of metabolic enzymes; biophysical studies of disease-related missense variants

Research Description

Our laboratory studies the three-dimensional structures of metabolic enzymes, including those relevant to human disease and plant-pathogen interactions. A major focus of the lab is characterizing proteins in an enzyme superfamily known as the alpha-D-phosphohexomutases.  These enzymes catalyze the production of phosphorylated sugar precursors that are assembled into more complex carbohydrates, such as polysaccharides.  Enzymes in this superfamily are found in all organisms, including bacteria, archaea, and eukaryotes.  In many bacteria, polysaccharides are critical determinants of infectivity, and so these enzymes are excellent targets for the design of antimicrobial agents. We have conducted detailed structure-function analyses using methods including X-ray crystallography, kinetics, small angle X-ray scattering, and hydrogen deuterium exchange.  These studies include enzymes from important human pathogens, including P. aeruginosa, B. anthracis, and S. typhimurium.  In humans, deficiency in the enzyme phosphoglucomutase 1 (PGM1) has been recently identified as an inherited metabolic disease categorized as both a muscle glycogenosis (type XIV) and a congenital disorder of glycosylation (CDG types I and II). A better understanding of the molecular bases of this inherited disease should benefit patient prognosis and therapy.

A recent collaboration with plant scientist Melissa Mitchum focuses on studies of a soybean enzyme involved in folate metabolism.  Mutations in this enzyme, serine hydroxymethyltransferase 8 (SHMT8), are associated with resistance to the devastating pathogen soybean cyst nematode (SCN).  Structural biochemical studies have revealed that resistance to SCN infection is linked to impaired binding of folate to SHMT8. Ongoing studies include developing new ways to engineer SCN resistance to help combat this critical agricultural pathogen.

Notable Honors and Service

  • Session chair, 2018 annual meeting of the American Crystallographic Association
  • Editor, Acta Crystallographica F:  Structural Biology and Crystallization Communications, 2009-2017
  • Chair, BIOMAC Special Interest Group American Crystallographic Association
  • Program Director, Annual meeting of the American Crystallographic Association, 2004

Selected Publications

Stiers KM, Hansen RP, Daghlas BA, Mason KN, Zhu JS, Jakeman DL, Beamer LJ. (2020). A missense variant remote from the active site impairs stability of human phosphoglucomutase 1. J Inherit Metab Dis. 2020 Feb 14. doi: 10.1002/jimd.12222. Epub ahead of print. [PubMed]

Korasick DA, Kandoth PK, Tanner JJ, Mitchum MG, Beamer LJ. (2020). Impaired folate binding of serine hydroxymethyltransferase 8 from soybean underlies resistance to the soybean cyst nematode. J Biol Chem. 2020 Feb 2. doi: 10.1074/jbc.RA119.012256. Epub ahead of print. [PubMed]

Zhu JS, Stiers KM, Soleimani E, Groves BR, Beamer LJ, Jakeman DL. (2019). Inhibitory Evaluation of αPMM/PGM from Pseudomonas aeruginosa: Chemical Synthesis, Enzyme Kinetics, and Protein Crystallographic Study. J Org Chem. 84(15):9627-9636. doi: 10.1021/acs.joc.9b01305. [PubMed]

Stiers KM, Graham AC, Zhu JS, Jakeman DL, Nix JC, Beamer LJ. (2019). Structural and dynamical description of the enzymatic reaction of a phosphohexomutase. Struct Dyn. 6(2):024703. doi: 10.1063/1.5092803. eCollection 2019 Mar. [PubMed]

Radenkovic S, Bird MJ, Emmerzaal TL, Wong SY, Felgueira C, Stiers KM, Sabbagh L, Himmelreich N, Poschet G, Windmolders P, Verheijen J, Witters P, Altassan R, Honzik T, Eminoglu TF, James PM, Edmondson AC, Hertecant J, Kozicz T, Thiel C, Vermeersch P, Cassiman D, Beamer L, Morava E, Ghesquière B. (2019). The Metabolic Map into the Pathomechanism and Treatment of PGM1-CDG. Am J Hum Genet. 104(5):835-846. doi: 10.1016/j.ajhg.2019.03.003. [PubMed]

Stiers KM, Beamer LJ. (2018). A Hotspot for Disease-Associated Variants of Human PGM1 Is Associated with Impaired Ligand Binding and Loop Dynamics. Structure. 26(10):1337-1345.e3. doi: 10.1016/j.str.2018.07.005. [PubMed]

Xu J, Sarma AVS, Wei Y, Beamer LJ, Van Doren SR. (2017). Multiple Ligand-Bound States of a Phosphohexomutase Revealed by Principal Component Analysis of NMR Peak Shifts. Sci Rep. 7(1):5343. doi: 10.1038/s41598-017-05557-w. [PubMed]

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