Lesa J. Beamer, PhD

Professor

Biochemistry
Chemistry

Contact Information

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

Education

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

Research Area

Structural biology: X-ray crystallography of medically important proteins.

Research Description

Our laboratory studies the three-dimensional structures of proteins relevant to human disease. 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. 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).

In studies of the bacterial members of the superfamily, 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.  We have also utilized computational analyses, such as normal mode and co-evolutionary analyses to better understand the relationships between protein structure, conformational flexibility, and sequence relationships in the family. In collaboration with the laboratory of Steven Van Doren, we are characterizing the role of protein dynamics in the mechanism of P. aeruginosa PMM/PGM via NMR.  Insights from our recent studies include a key role for phosphorylation of the active site serine in both catalysis and enzyme flexibility. Our recent work on human PGM1 includes biochemical and structural characterization of missense variants associated with disease.  A better understanding of the molecular bases of this inherited disease should benefit patient prognosis and therapy.

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

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]

Zhu JS, Stiers KM, Winter SM, Garcia AD, Versini AF, Beamer LJ, Jakeman DL. (2019). Synthesis, Derivatization, and Structural Analysis of Phosphorylated Mono-, Di-, and Trifluorinated d-Gluco-heptuloses by Glucokinase: Tunable Phosphoglucomutase Inhibition. ACS Omega. 4(4):7029-7037. doi: 10.1021/acsomega.9b00008. [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). Assessment and Impacts of Phosphorylation on Protein Flexibility of the α-d-Phosphohexomutases. Methods Enzymol. 607:241-267. doi: 10.1016/bs.mie.2018.04.003. [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]

Stiers KM, Xu J, Lee Y, Addison ZR, Van Doren SR, Beamer LJ. (2017). Phosphorylation-Dependent Effects on the Structural Flexibility of Phosphoglucosamine Mutase from Bacillus anthracis. ACS Omega. 2(11):8445-8452. doi: 10.1021/acsomega.7b01490. eCollection 2017 Nov 30. [PubMed]

Muenks AG, Stiers KM, Beamer LJ. (2017). Sequence-structure relationships, expression profiles, and disease-associated mutations in the paralogs of phosphoglucomutase 1. PLoS One. 12(8):e0183563. doi: 10.1371/journal.pone.0183563. eCollection 2017. [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]

Stiers KM, Muenks AG, Beamer LJ. (2017). Biology, Mechanism, and Structure of Enzymes in the α-d-Phosphohexomutase Superfamily. Adv Protein Chem Struct Biol. 109:265-304. doi: 10.1016/bs.apcsb.2017.04.005. [PubMed]

Korasick DA, Gamage TT, Christgen S, Stiers KM, Beamer LJ, Henzl MT, Becker DF, Tanner JJ. (2017). Structure and characterization of a class 3B proline utilization A: Ligand-induced dimerization and importance of the C-terminal domain for catalysis. J Biol Chem. 292(23):9652-9665. doi: 10.1074/jbc.M117.786855. [PubMed]

Stiers KM, Graham AC, Kain BN, Beamer LJ. (2017). Asp263 missense variants perturb the active site of human phosphoglucomutase 1. FEBS J. 284(6):937-947. doi: 10.1111/febs.14025. [PubMed]

Lee Y, Furdui C, Beamer LJ. (2016). Data on the phosphorylation state of the catalytic serine of enzymes in the α-D-phosphohexomutase superfamily. Data Brief. 10:398-405. doi: 10.1016/j.dib.2016.12.017. eCollection 2017 Feb. [PubMed]

Stiers KM, Lee CB, Nix JC, Tanner JJ, Beamer LJ. (2016). Synchrotron-based macromolecular crystallography module for an undergraduate biochemistry laboratory course. J Appl Crystallogr. 49(Pt 6):2235-2243. eCollection 2016 Dec 1. [PubMed]

Wong SY, Beamer LJ, Gadomski T, Honzik T, Mohamed M, Wortmann SB, Brocke Holmefjord KS, Mork M, Bowling F, Sykut-Cegielska J, Koch D, Ackermann A, Stanley CA, Rymen D, Zeharia A, Al-Sayed M, Marquardt T, Jaeken J, Lefeber D, Conrad DF, Kozicz T, Morava E. (2016). Defining the Phenotype and Assessing Severity in Phosphoglucomutase-1 Deficiency. J Pediatr. 175:130-136.e8. doi: 10.1016/j.jpeds.2016.04.021. [PubMed]

Stiers KM, Kain BN, Graham AC, Beamer LJ. (2016). Induced Structural Disorder as a Molecular Mechanism for Enzyme Dysfunction in Phosphoglucomutase 1 Deficiency. J Mol Biol. 428(8):1493-505. doi: 10.1016/j.jmb.2016.02.032. [PubMed]

Xu J, Lee Y, Beamer LJ, Van Doren SR. (2015). Phosphorylation in the catalytic cleft stabilizes and attracts domains of a phosphohexomutase. Biophys J. 108(2):325-37. doi: 10.1016/j.bpj.2014.12.003. [PubMed]


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