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Jun-Yong Choe, PhD

Assistant Professor

Dr. Jun-Yong Choe received his master's degree in 1997 and his PhD in 2001, both from Iowa State University.

Dr. Choe worked as a postdoctoral fellow at the California Institute of Technology from 2002 to 2004, a research associate at Howard Hughes Medical Institute from 2003 to 2004, a senior crystallographer at the University of Toronto's Structural Genomics Consortium from 2004 to 2005, and an assistant research physiologist at the University of California, Los Angeles from 2005 to 2007.

Research

My research interest involves structural and functional studies of membrane proteins, originating from prokaryotic and eukaryotic organisms, using x-ray crystallography. Membrane proteins mediate the cell exchange of energy, nutrients and information and, thus, are targets for a majority of the prescribed drugs (50% of drugs on the market target membrane proteins). Although, 25% of the proteins in genomes are membrane proteins, less than 1% of their structures are known. I am typically interested in secondary transport proteins among membrane proteins. They are highly relevant to human physiology and disease (eg. depression, diabetes, multidrug resistance). Also of note, at least two widely prescribed drugs [fluoxetine (Prozac) and omeprazole (Prilosec)], are targeted to membrane-transport proteins. Despite the utter medical importance of membrane proteins, the molecular basis of their function has been and continues to be an arduous task. Since the study of membrane proteins is challenging, the chances of success can be increased with the number of trials, specifically by implementing high throughput methodology in protein expression and crystallization.

Carbohydrate transporters

Carbohydrates serve as basic fuel molecules for eukaryotic cells. These molecules are unable to freely diffuse across cellular membranes but instead require transporter proteins to either enter or exit cells. Carbohydrate transporters have similar structures, consisting of 12 transmembrane helixes. Aberrant transporter genes are the cause of several congenital defects of sugar metabolism (GLUT1 deficiency and Fanconi-Bickel syndromes), and a malfunction of glucose transporter expression or regulation (GLUT4) appears to contribute to the insulin resistance syndrome. In animal models of type II non-insulin dependent diabetes, a decrease in the levels of GLUT2 in the pancreatic cells precedes the development of diabetes. Homologous proteins of human GLUT were crystallized (see BMB website) and the structural determination is ongoing.

Proteins are dynamic systems and in order to understand the molecular basis of their function, it is important to determine the structures of several of their different key conformations. For example, below movie of Fructose-1,6-bisphosphatase (FBPase; a key gluconeogenic cytosolic phosphatase) represented the changes in protein conformation as it goes through the apo, substrates-, intermediate-, and product-bound states. The FBPase crystal structures in these different ligation stages were solved.

The movie of Lactose permease (the membrane transporter for lactose) also represented different stages of the protein action, however, currently, only one conformation is known. The dynamics shown in the movie is based on electron spin resonance studies corroborated with the available crystal structure showing the distance changes between specific spin labels in dynamic domains while the protein is transporting lactose.

Fructose-1,6-bisphosphatase: Lactose permease:

Publications

  • Smirnova, I., Kasho, V., Sugihara, J., Choe, J., and Kaback, H.R., (2009) "Residues in the H+ translocation site define the pKa for sugar binding to LacY." Biochemistry, 48, 8852-8860. [medline]
  • Moiseeva, N., Bau, R., Swensson, S.D., Markland, F.S., Choe, J., Liu, Z.J., Allaire. M., (2008) "Crystal structure of Acostatin, a dimeric disintegrin from Southern copperhead (Agkistrodon contortrix contortrix) at 1.7 Å resolution." Acta Cryst. D 64, 466-70. [medline]
  • Smirnova, I., Kasho, V., Choe, J., Altenbach, C., Hubbell, W.L., and Kaback, H.R., (2007) “Sugar binding induces an outward facing conformation of LacY." Proc. Natl. Acad. Sci. USA. 104, 16504-9. [medline]
  • Lee, J., Kang, H., Moon, Y., Cho, D., Kim, D., Choe, J.Y., Honzatko, R.B., and Robyt, J.F., (2006) “Cloning, Expression, and Characterization of an Extracellular Enolase from Leuconostoc mesenteroides." FEMS Microbiol. Lett. 259, 240-8. [medline]
  • Choe, J., Dimov, S., Arrowsmith, C., Edwards, A., Sundstrom, M., Bochkarev, A., Park, H., (2005 “Structure of Human Nucleoside-Diphosphate Kinase 3 (Protein Data Bank Identification Code: 1ZS6)", Structural Genomics Consortium. [sgc entry]
  • Choe, J., Artz, J.D., Gao, M., Lew, J., Zhao, Y., Arrowsmith, C., Edwards, A., Sundstrom, M., Bochkarev, A., Hui, R., (2005) “Structure of Nuclear transport factor 2 (Ntf2) from Cryptosporidium Parvumuman (Protein Data Bank Identification Code: 1ZO2)", Structural Genomics Consortium. [sgc entry]
  • Choe, J., Atanassova, A., Arrowsmith, C., Edwards, A., Sundstrom, M., Bochkarev, A., Park, H., (2005) “Structure of Human Muscle Pyruvate Kinase (Protein Data Bank Identification Code: 1ZJH)", Structural Genomics Consortium. [sgc entry]
  • Choe, J., Atanassova, A., Arrowsmith, C., Edwards, A., Sundstrom, M., Bochkarev, A., Park, H., (2005) “Structure of Human Adenylate Kinase 3 Like 1 (Protein Data Bank Identification Code: 1ZD8)", Structural Genomics Consortium. [sgc entry]
  • Mulichak, A.M., Lew, J., Artz, J., Choe, J., Walker, J.R., Zhao, Y., Sundstrom, M., Arrowsmith, C., Edwards, A., Bochkarev, A., Hui, R., Gao, M., (2005) “Crystal Structure of Guanylate Kinase from Plasmodium Falciparum (Protein Data Bank Identification Code: 1Z6G)", Structural Genomics Consortium. [sgc entry]
  • Choe, J., Atanassova, A., Arrowsmith, C., Edwards, A., Sundstrom, M., Bochkarev, A., Park, H., (2005) “Structure of Human ADP-Ribosylation Factor-Like 10B (Protein Data Bank Identification Code: 1ZD9)", Structural Genomics Consortium. [sgc entry]
  • Choe, J., Atanassova, A., Arrowsmith, C., Edwards, A., Sundstrom, M., Bochkarev, A., Park, H., (2005) “Structure of Human ADP-Ribosylation Factor-Like 5 (Protein Data Bank Identification Code: 1Z6Y)", Structural Genomics Consortium. [sgc entry]
  • Choe, J., Atanassova, A., Arrowsmith, C., Edwards, A., Sundstrom, M., Bochkarev, A., Park, H., (2005) “Structure of Human ADP-Ribosylation Factor 4 (Protein Data Bank Identification Code: 1Z6X)",Structural Genomics Consortium. [sgc entry]
  • Walker, J.R., Choe, J., Avvakumov, G.V., Newman, E.M., Mackenzie, F., Sundstrom, M., Arrowsmith, C., Edwards, A., Bochkarev, A., Dhe-Paganon, S., (2005) “Structure of Novel Ubiquitin-Conjugating Enzyme (Protein Data Bank Identification Code: 1YRV)", Structural Genomics Consortium. [sgc entry]
  • Choe, J., Atanassova, A., Arrowsmith, C., Edwards, A., Sundstrom, M., Bochkarev, A., Park, H., (2005) “Structure of Human ADP-Ribosylation Factor-Like 8 (Protein Data Bank Identification Code: 1YZG)", Structural Genomics Consortium. [sgc entry]
  • Choe, J., Avvakumov, G.V., Newman, E.M., Mackenzie, F., Kozieradzki, I., Bochkarev, A., Sundstrom, M., Arrowsmith, C., Edwards, A., Dhe-Paganon, S., (2005) “Structure of Ubiquitin-Conjugating Enzyme E2-25KDa (Huntington Interacting Protein 2; Protein Data Bank Identification Code: 1YLA)", Structural Genomics Consortium. [sgc entry]
  • Choe, J.Y., Iancu, C.V., Fromm, H.J., and Honzatko, R.B. (2003) "Metaphosphate in the Active Site of Fructose-1,6-bisphosphatase." J. Biol. Chem. 278, 16015-20.
  • Choe, J.Y., Nelson, S.W., Fromm, H.J., and Honzatko, R.B. (2003) "Interaction of Tl+ with Product Complexes of Fructose-1,6-bisphosphatase." J. Biol. Chem. 278, 16008-14.
  • Choe, J.Y., Nelson, S.W.,Arienti, K.L., Axe,F.U., Collins,T.L., Jones,T.K.,Kimmich,R.D.,Michael ,J., Newman, M.L., Norvell, K., Ripka, W.C., Romano, S.J., Short,K.M., Slee,D.H., Fromm,H.J., and Honzatko,R.B. (2003) "Inhibition of Fructose-1,6-bisphosphatase by a New Class of Allosteric Effectors." J. Biol. Chem. 278, 51176-83.
  • Park, M., Ryu, J., Kim, D., Choe, J., and Robyt, J.F. (2001) "Characterization of Leuconostoc mesenteroides B-742CB Dextransucrase Expressed in Escherichia coli." J. Microbiol. Biotechnol. 11, 628-635.
  • Iancu, C.V., Borza, T., Choe, J.Y., Fromm, H.J., and Honzatko,R.B. (2001) "Recombinant mouse muscle adenylosuccinate synthetase: overexpression, kinetics, and crystal structure." J. Biol. Chem. 276, 42146-52.
  • Nelson, S.W., Iancu, C.V., Choe, J.Y., Honzatko, R.B., and Fromm, H.J. (2000)"Tryptophan fluorescence reveals the conformational state of a dynamic loop in recombinant porcine fructose-1,6-bisphosphatase." Biochemistry 39, 8565-73.
  • Nelson, S.W., Choe, J.Y., Honzatko,R.B., and Fromm, H.J. (2000) "Mutations in the hinge of a dynamic loop broadly influence functional properties of fructose-1,6 bisphosphatase." J. Biol Chem. 275, 29986-92.
  • Choe, J.Y., Fromm, H.J., and Honzatko, R.B. (2000) "Crystal structures of fructose-1,6-bisphosphatase: mechanism of catalysis and allosteric inhibition revealed in product complexes." Biochemistry 39, 8565-74.
  • Choe, J.Y., Poland, B.W., Fromm, H.J., and Honzatko, R.B.(1999) "Mechanistic implications from crystalline complexes of wild-type and mutant adenylosuccinate synthetases from Escherichia coli." Biochemistry 38, 6953-61.
  • Choe, J.Y., Poland, B.W., Fromm, H.J., and Honzatko, R.B. (1998) "Role of conformationaly dynamic loop in cation activation and allosteric regulation of recombinant porcine fructose-1,6-bisphosphatase." Biochemistry 37, 11441-50.
  • Ferutz, K., Choe, J.Y., Honzatko, R.B., and Fromm, H.J. (1998) "Directed mutations in the poorly defined region of porcine liver fructose 1,6 bisphosphatase significantly affects catalysis and the mechanism of AMP inhibition." J. Biol Chem. 273, 17511-6.
  • Robyt, J.F., Choe, J., Hahn, R.S., Fox, J.D. and Fuchs, E.B. (1996) "Acid modification of starch granules in alcohols: reactions in mixtures of two alcohols combined in different ratios." Carbohydrate Research 283, 141-50.