Cellular and Molecular Biochemistry Unit, OPCB
NATIONAL INSTITUTES OF HEALTH/NIDCR
BUILDING 30 ROOM 211
30 CONVENT DR MSC 4340
BETHESDA MD 20892-4340
Phone: (301) 496-4069
Fax: (301) 402-0823
E-mail: Dr. Myung Hee Park
Research Interests
The goal of this Unit is the understanding of molecular structure/biological function relationships. Its major emphasis has been centered around enzymes involved in a unique posttranslational modification reaction resulting in the formation of the unusual amino acid hypusine in a single cellular protein, eukaryotic translation initiation factor 5A (eIF5A). The essential role of the hypusine modification in the activity of eIF5A and in eukaryotic cell proliferation has now been demonstrated in studies in yeast and mammalian cells by genetic and pharmacological approaches. The biosynthetic pathway of hypusine which involves two enzymes, deoxyhypusine synthase and deoxyhypusine hydroxylase, has been revealed through the Unit’s efforts and the two enzymes have been cloned and characterized. Potent inhibitors of the first step enzyme, deoxyhypusine synthase, have been developed and shown to exert strong antiproliferative effects on normal and cancer cells. These findings have furthered the knowledge of the role of hypusine modification and offered a potential mechanism for control of normal and aberrant cell growth.
Education
B.S. Seoul National University 1972
Ph.D. Brown University 1977
Recent publications
Park, J-H, Aravind, L, Wolff, EC, Kaevel, J, Kim, YS and Park MH (2006) Molecular cloning, expression and structural prediction of deoxyhypusine hydroxylase: a novel HEAT-repeat-containing metalloenzyme, Proc. Natl. Acad. Sci. USA, 103, 51-56.
Park, MH (2006) The post-translational synthesis of a polyamine-derived amino acid, hypusine, in the eukaryotic translation initiation factor 5A (eIF5A) J. Biochem., 139, 1-9
Kim YS, Kang KR, Wolff EC, Bell JK, McPhie P and Park MH. Deoxyhypusine hydroxylase is a Fe(II)-dependent HEAT-repeat enzyme: Identification of amino acid residues critical for Fe(II) binding and catalysis. J. Biol. Chem. 2006:281:13217-25
Clement, P. M. J., Johansson, H. E., Wolff, E. C. and Park MH. Differential expression of eIF5A-1 and eIF5A-2 in human cancer cells. FEBS J. 2006:273: 1102-14.
Umland TC, Wolff EC, Park MH and Davies DR (2004) A new crystal structure of deoxyhypusine synthase reveals the configuration of the active site enzyme and of an enzyme:NAD:inhibitor ternary complex. J. Biol. Chem. 279, 28697-28705
Park J-H, Wolff EC, Folk JE and Park MH (2003) Reversal of the deoxyhypusine synthesis reaction: Generation of spermidine or homospermidine from deoxyhypusine by deoxyhypusine synthase. J. Biol. Chem. 278, 32683-32691
Clement PMJ, Hanauske-Abel HM, Wolff EC, Kleinman HK and Park MH (2002) The antifungal drug ciclopirox inhibits deoxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro. Int. J. Cancer 100, 491-498
Wolff EC, Wolff J and Park MH (2000): Deoxyhypusine synthase generates and uses bound NADH in a transient hydride transfer mechanism. J. Biol. Chem. 275, 9170-9177
Park MH, Joe YA and Kang KR (1998) Deoxyhypusine synthase activity is essential for cell viability in the yeast Saccharomyces cerevisiae J. Biol. Chem. 273: 1677-1683
Joe YA, Wolff EC, Lee YB and Park MH (1997) Enzyme-substrate intermediate at a specific lysine residue is required for deoxyhypusine synthesis: the role of Lys329 in human deoxyhypusine synthase J. Biol. Chem. 272: 32679-326785