College of Computer, Mathematical, and Natural Sciences

Norma Allewell

Dr. Norma Allewell

Professor 

Contact

Office Phone: (301) 405-1302
Fax: (301) 314-9489
Office Address: 1125 Microbiology

Graduate Program Affiliations

  • BISI - BISI-Molecular & Cellular Biology (MOCB)

Research Interests

We study the functional mechanisms and role in health and disease of multisubunit proteins involved in nitrogen metabolism. Binding of ligands typically causes changes in tertiary structure and subunit interactions that mediate and regulate their biological activity. We use X-ray crystallography, computer modeling and genetic, physical biochemical and enzymological approaches to understand the relationship between structure and function and to determine how naturally mutations alter function and cause disease. Current research focuses on enzymes of the urea cycle in humans and arginine biosynthesis in micro-organisms and plants. Mutations in these enzymes often cause clinical hyperammonemia resulting in neurological symptoms or even death. In collaboration with Dr. Mendel Tuchman and his colleagues at Children’s National Medical Center in Washington, DC, we have focused on ornithine transcarbamlyase (OTCase) and N-acetyl-L-glutamate synthase (NAGS). We also discovered novel biochemical pathways for arginine biosynthesis in bacteria and characterized the enzymes involved both biochemically and structurally. Current research focuses on the mechanism by which NAGS acts as a master regulator of the urea cycle and the development of new treatments for treating disorders of the urea cycle.

Recent Publications

Crystal Structure of the N-acetyltransferase domain of human N-acetyl-L-glutamate synthase in complex with N-acetyl-L-glutamate provides insights into its catalytic and regulatory mechanisms.  Zhao, G., Jin, Z., Allewell, N. M., Tuchman, M., Shi D. PLoS ONE 8(7): 370369 (2013)

Structure and function of Escherichia coli RimK, an ATP-grasp fold, L-glutamyl ligase enzyme.  Zhao, G., Jin, Z., Wang, Y., Allewell, N. M., Tuchman, M., Shi, D. Proteins 81, 1847-54 (2013)

Structure of the complex of Neisseria gonorrhoeae N-acetyl-L-glutamate synthase with a bound bisubstrate analog.  Zhao, G., Allewell., N. M., Tuchman, M., Shi, D. Biochem. Biophys. Res. Commun. 430, 1258-3 (2013)

Structure and function of the complex of Neisseria gonorrhoeae N-acetyl-L-glutamate synthase with a bound bisubstrate analog. Zhao, G., Allewell, N.M., Tuchman, M., Shi, D. Biochem. Biophys. Res. Comm. (2013) 430, 1253-8.

Molecular Biophysics for the Life Sciences. N. M. Allewell, L. Narhi, I. Rayment, Springer, 2013.

Crystal structure and biochemical properties of putrescine carbamoyltransferase from Enterococcus faecalis: assembly, active site and allosteric regulation. Shi, D., Yu, X., Zhao, G, Ho, J., Lu, S., Allewell, N.M., Tuchman M. Proteins (2012) 80, 1436-47.

Thematic minireview series on enzyme evolution in the post-genomic era. Allewell N.M. J. Biol. Chem. (2012) 287, 1-2.

A novel N-acetylglutamate synthase architecture revealed by the crystal structure of the bifunctional enzyme from Maricaulis maris. Shi, D., Li, Y., Cabrera-Luque, J., Jin, Z., Yu, X., Zhao, G., Haskins, N., Allewell, N.M., Tuchman, M. PLoS (2011), 6(12):E28825.

The ygeW encoded protein from Escherichia coli is a knotted ancestral catabolic transcarbamylase. Li, Y., Jin, Z., Yu, X., Allewell, N.M., Tuchman, M., Shi, D. Proteins (2011) 79, 2327-34.

Mechanism of allosteric inhibition of N-acetyl-L-glutamate synthase by L-arginine. Min, L., Jin, Z., Caldovic, L., Morizono, H., Allewell, N.M., Tuchman, M., Shi, D., J. Biol. Chem. (2009) 284, 4873-80.

Shi, D., Morizono, H., Cabrera-Luque, J., Yu, X., Roth, L., Malamy, M. H., Allewell, N. M.,and Tuchman, M. Structure and Catalytic Mechanism of a Novel N-Succinyl-L-ornithine Transcarbamylase in Arginine Biosynthesis of Bacteroides fragilis. J. Biol. Chem. 281, 20623-20631 (2006)

Shi, D., Sagar, V., Jin, Z., Yu, X., Caldovic, L., Morizono, H., Allewell, N. M.,and Tuchman, M. The Crystal Structure of N-Acetyl-L-Glutamate Synthase from N. gonorrhoeae Provides Insights into Mechanisms of Catalysis and Regulation.  J. Biol. Chem. 283, 7176-7184 (2008).

Awards

  • Fellow, American Association for the Advancement of Science, 1985
  • NIH MERIT Award, 1991
  • Emily M. Gray Award for Education, Biophysical Society, 2002
  • Doctor Scientiae, McMaster University, 2007

Education

  • B. Sc. (Hon), Biochemistry, McMaster University, 1965.
  • Ph. D., Molecular Biophysics, Yale University, 1969.
  • NIH NRSA fellow, Biophysical Chemistry, Yale University, 1969-70.

Previous Positions

  • Polytechnic Institute of Brooklyn, Assistant Professor, 1970-1973
  • Wesleyan University, Department of Biology, 1970-1984; Department of Molecular Biology and Biochemistry, 1984-1991
  • Instructor, Physiology course, Marine Biological Laboratories, Woods Hole, MA, summers of 1981-83
  • University of Minnesota, Department of Biochemistry: Professor, 1991-1998; Head, 1991-95
  • University of Maryland, Dean of Chemical and Life Sciences and Professor of Chemistry and Biochemistry, 2000-2010

 Major National Service 

  • President,Biophysical Society, 1993-4
  • Advisory Board, Protein Data Bank, Brookhaven National Laboratories, 1994-99; Chair,1997-98
  • U.S. National Committee for the International Union of Pure and Applied Biophysics,1995-99
  • National Research Council Space Studies Board Committee on Space Biology and Medicine,1995-2000
  • Board of Directors, Federation of American Societies for Experimental Biology, 1993-94; 2004-06 Biological Sciences Advisory Committee, NSF, 2003-06
  • Biological Sciences Advisory Committee, NSF, 2003-06
  • Journal of Biological Chemistry, Editorial Board, 1995-2000; Associate Editor, 2002-present
  • Board of Scientific Counselors, National Center for Biotechnology Information, National Library of Medicine, 2008-13
  • Jefferson Science Fellow, US Department of State, 2011-12.