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Aspartate Dehydrogenase

PSI-SGKB [doi:10.3942/psi_sgkb/fm_2008_8]
Featured System - August 2008
Short description: Aspartate dehydrogenase is a new enzyme discovered by Northeast Structural Genomics Consortium.

Aspartate dehydrogenase is a new enzyme discovered by Northeast Structural Genomics Consortium. The path to discovery began with the genome of the bacterium Thermotoga maritima, a bacterium found in geothermally-heated sediments in the ocean. The gene for this protein was interesting for several reasons. First, similar proteins are found in many other organisms, and thus the protein may play an important role in cellular function. Also, the gene was found as part of a larger operon that includes two enzymes that are involved in the synthesis of nicotinamide rings. Many other bacteria have a similar operon, but it usually includes a gene that encodes aspartate oxidase instead of this new protein. Based on this information, the protein was synthesized and crystallized, and the structure solved by x-ray crystallography.

Predicting Function from Structure

The structure of this protein revealed a small protein with NAD bound in a deep pocket. The fold of the protein is a familiar Rossmann fold, which is common in enzymes that use NAD in their reactions, suggesting that the protein may be a dehydrogenase. Based on these observations, the enzyme was tested for function with a variety of substrates and cofactors, and it was found to be a dehydrogenase that uses NAD to oxidize aspartate. Further testing showed that it is highly specific for aspartate and doesn't oxidize the similar amino acids glutamate and asparagine. Based on these results, the new enzyme was named "asparate dehydrogenase."

Building NAD with NAD

Our own cells are not able to build the nicotinamide ring in NAD, so we have to obtain this essential molecule in our diet as a vitamin. Most bacteria, however, are able to build it from scratch. The first step in this process is the oxidation of aspartate to iminoaspartate, which will ultimately form half of the nicotinamide ring. We now know that bacteria can use (at least) two ways to perform this reaction. Some bacteria use the enzyme aspartate oxidase, which uses an FAD cofactor and oxygen or fumarate. This new structure revealed that other bacteria, such as Thermotoga maritima, use a different route, using NAD as a cofactor in the first step towards creation of more NAD.

Looking at the Structure

You can take a closer look at this enzyme in PDB entry 1j5p. The enzyme is a symmetrical complex of two subunits, with two identical active sites on opposite sides of the dimer. The active site of aspartate dehydrogenase is found in a deep pocket that holds the NAD cofactor and the substrate. A nearby histidine amino acid (shown in magenta in the Jmol image below) is proposed to be an important catalytic residue.

The JSmol tab below displays an interactive JSmol view

Lambda cII Protein (PDB entry 1zs4)

The lambda cII protein uses several different methods to recognize its promoter sequence in the DNA. In this picture, the DNA-binding domain of the protein is shown in blue, and the two DNA strands are shown in pink and orange, with the four base pairs in the recognition sequence in bright colors, and the flanking regions darkened. Four sidechains from the protein extend into the major groove and form hydrogen bonds with the bases. Two water molecules (red spheres) are also positioned by the pro


  1. Z. Yang, A. Savchenko, A. Yakunin, R. Zhang, A. Edwards, C. Arrowsmith and L. Tong. (2003) Aspartate dehydrogenase, a novel enzyme identified from structural and functional studies of TM1643. Journal of Biological Chemistry 278, 8804-8808.

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health