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Dashuang Shi Dashuang Shi
Adjunct Research Professor of Genomics and Precision Medicine
Adjunct Research Professor of Pediatrics (Secondary)

Office Phone: 202-476-6029
Email: Email
Department: Genomics and Precision Medicine

Education

  • BS, Xiamen University, China, 1983
  • MS, Xiamen University, China, 1987
  • PhD, University of Sydney, Australia, 1997

Biography

I was fascinated by the beauty of crystals since I was a high school student.  I was then pursuing this interest with outstanding mentors, first at Xiamen University (Shengzhi Hu’s lab 1983-87), and then as a Ph.D. student at University of Sydney (Hans Freeman’s lab 1991-96). For a post-doc, I worked with Norma Allewell at University of Minnesota on structural and functional studies of ornithine transcarbamylase and ferritin.  My laboratory has continued to work on structures/function relationships on some important nitrogen metabolism related enzymes, particularly in urea cycle and arginine biosynthetic pathway.

Additional Education

University of Minnesota  Post-Doc 1996-1999 Crystallography

Bibliography

Selected From 40:  Peer-reviewed (38); Solicited (2):

  • Shi, D., Morizono, H., Ha, Y., Aoyagi, M., Tuchman, M. and Allewell, N.M. (1998) 1.85 Å resolution crystal structure with human ornithine transcarbamoylase complxed with N-phosphonacetyl-L-ornithine: catalytic mechanisms and correlation with ornithine transcarbamoylase deficiency. J. Biol. Chem. 273, 34247-34254.
     
  • Takagi, H., Shi, D., Ha, Y., Allewell, N.M. and Theil, E.C. (1998) Localized unfolding at the Junction of three ferritin subunits. J. Biol. Chem. 273, 18685-18688.
     
  • Allewell, N.M., Shi, D., Morizono, H. and Tuchman, M. (1999) Molecular recognition by ornithine and aspartate transcarbamoylases, Account of Chemical Research 32, 885-894.
     
  • Shi, D., Gallegos, R., DePonte, J., Morizono, H., Yu, X., Allewell, N.M., Malamy, M. and Tuchman, M. (2002).  Crystal structure of a transcarbamylase-like protein from bacteroides fragilis at 2.0Å resolution. J. Mol. Biol. 320, 899-908.
     
  • Shi, D., Morizono, H., Yu, X., Roth, L., Caldovic, L., Allewell, N.M., Malamy, M.H. and Tuchman M. (2005) Crystal structure of N-acetylornithine transcarbamylase from Xanthomonas campestris: a novel enzyme in a new arginine biosynthetic pathway found in several eubacteria. J. Biol. Chem. 280, 14366-14369.
     
  • Shi, D., Morizono, H., Cabrera-Luque, J., Yu, X., Roth, L., Malamy, M.H., Allewell, N.M. and Tuchman, M.. (2006) Structure and mechanism of a novel N-succinyl-L-ornithine trasncarbamoylase in arginine biosynthesis of Bacteroides fragilis. J. Biol. Chem. 281, 20623-20631.
     
  • Shi, D., Yu, X., Cabrera-Luque, J., Chen, T., Roth, L., Morizono, H., Allwell, N. M. and Tuchman, M. (2007) A single mutation in the active site swaps the substrate specificity of N-acetyl-L-ornithine transcarbamylase and N-succinyl-L-ornithine transcarbamylase. Protein Sci. 16, 1689-1699.
     
  • Shi, D., Sagar, V., Jin, Z., Yu, X., Caldovic, L., Morizono, H., Allewell, N. M. and Tuchman, M. (2008) The Crystal Structure of N-Acetyl-L-glutamate Synthase from Neisseria gonorrhoeae Provides Insights into Mechanisms of Catalysis and Regulation. J. Biol. Chem. 283, 7176-7184.
     
  • Min, Li., Jin, Z., Caldovic, L., Morizono, H., Allewell, N.M., Tuchman, M. and Shi, D. (2009) Mechanism of allosteric inhibition of N-acetyl-glutamate synthase by L-arginine. J. Biol. Chem. 284, 4873-4880.
     
  • Ou, W., King, H., Delisle, J., Shi, D., Wilson, C.A. (2009) Phenylalanines at positions 88 and 159 of Ebolavirus envelope glycoprotein differentially impact envelope function. Virology, 396, 135-142.

Research

Structures and function of N-acetyl-L-glutamate synthase: N-acetyl-L-glutamate synthase (NAGS) catalyzes the acetylation of L-glutamate to produce N-acetyl-L-glutamate which is an obligatory allosteric activator of carbamylphosphate synthetase I in the urea cycle in mammals. The reaction is also the first committed step of arginine biosynthesis in most microorganisms and plants. Until recently, no structure of any NAGS protein was available due to the recalcitrant nature of the protein to crystallization and poor X-ray diffraction quality. We are now able to crystallize and solve the three dimensional NAGS structure from Neisseria gonohorreae (ngNAGS), which is closely related to E. coli and other bacterial NAGS. Four structures at high resolution (better than 2.5 Å), with the substrates (CoA, AcCoA, L-glutamate and NAG) and the effector (L-arginine) bound, provided insights into the catalytic and arginine regulatory mechanisms of the NAGS enzyme. We will extend our structural studies to other NAGS which is closely related to mammalian NAGS.

Structures and function of transcarbamylase: The transcarbamylase superfamily of enzymes catalyzes the transfer of a carbamyl group from carbamyl phosphate (CP) to an amino group of a second substrate. Aspartate transcarbamylase (ATCase) and ornithine transcarbamylase (OTCase) are the two best-known members of this family. There are now more than 1000 transcarbamylase sequences known in the Pfam database. Most of them are either ATCases or OTCases, forming two major branches in the phylogenetic tree. However, several small clades exist between the root and the OTCase or ATCase branch. Our recent structural studies found that the transcarbamylases in these small clades are not OTCase or ATCase. Instead, two of them are novel N-acetyl-L-ornithine transcarbamylase (AOTCase) and N-succinyl-L-ornithine transcarbamylase (SOTCase), which have not been known previously. We will carry out a systematical genome-wide analysis of the transcarbamylase superfamily to classify the transcarbamylase into subfamilies, and to define the amino acid signatures common to the transcarbamylases and specific to each member on the basis of functional and structural features.

Link to pubmed publications: http://www.ncbi.nlm.nih.gov/pubmed/?term=dashuang+shi

Publications

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Industry Relationships and Collaborations

This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.

  • None