Dr. Mendel Tuchman

My laboratory is engaged in translational research of genes and proteins involved in nitrogen metabolism, in order to better
understand and treat patients with urea cycle disorders and hyperammonemia. We are studying the molecular and cell biology and
biochemistry of the urea cycle proteins. After solving the crystal structure of human ornithine transcarbamylase (OTC) deficiency and
exploring structure/function correlations, we are now investigating the mitochondrial ornithine transporter (ORNT1) as well as the
citrin (glutamate/aspartate) transporter and interactions with the OTC enzyme. Following the cloning of two mammalian
N-acetylglutamate (NAGS) genes and the identification of mutations in the human gene that cause hyperammonemia, we are now
working on the characterization of the "mature" recombinant enzyme(s) and the 3-D structure. We will also be investigating the
biological role of NAGS and its possible interactions with other components of the urea cycle and we are working to create an
animal model of NAGS deficiency.

Caldovic L, Tuchman M (2003) N-acetylglutamate and its role through evolution. Biochem J 372:279-290

Caldovic L, Morizono M, Panglao M, Cheng SF, Packman S, Tuchman M (2003) Null mutations in the N-acetylglutamate synthase gene associated with acute
neonatal disease and hyperammonemia. Hum genet 112:364-368

Caldovic L, Morizono H, Panglao MG, Gallegos R, Yu X, Shi D, Malamy MH, Norma M. Allewell NM, Tuchman M (2002) Cloning and expression of the human
N-acetylglutamate synthase gene. Biochem Biophys Res Commun 299:581-586

Caldovic L, Morizono H, Yu X, Thompson M, Shi D, Gallegos R, Allewell NM, Malamy MH, Tuchman M (2002) Identification, cloning and expression of the mouse
N-acetylglutamate synthase gene. Biochem J 364:825-831

Shi D, Gallegos R, DePonte J, Morizono H, Yu X, Allewell NM, Malamy M, Tuchman M (2002) Crystal structure of a new transcrbamylase from the anaerobic
bacterium Bacteroides fragilis at 2.0 Å resolution. J Mol Biol 320:899-908

Mavinakere M, Morizono H, Shi D, Allewell NM, Tuchman M (2001) The clinically variable R40H mutant ornithine transcarbamylase shows cytosolic degradation of
the precursor protein in CHO cells. J Inherit Metab Dis 24:614-622

Shi D, Morizono H, Yu X, Tong L, Allewell NM, Tuchman M (2001) Crystallization and preliminary x-ray crystallographic studies of wild-type human ornithine
transcarbamylase and two naturally occurring mutants at position 277. Acta Crystallogr D Biol Crystallogr 57:719-721

Shi D, Morizono H, Yu X, Allewell NM, Tuchman M (2001) Human ornithine transcarbamylase: Crystallographic insights into substrate recognition and
conformational change. Biochem J 354:501-509

Augustin L, Mavinakere M, Morizono H, Tuchman M (2000) Expression of wild type and mutant human ornithine transcarbamylase genes in Chinese hamster ovary
cells and study of dominant negative effect. Pediatr Res 48:842-846

Shi D, Morizono H, Aoyagi M, Tuchman M, Allewell NM (2000) Crystal structure of human ornithine transcarbamoylase complexed with carbamoyl phosphate and
L-norvaline at 1.9 Å resolution. Proteins 39:271-277