Crystal structure of Saccharomyces cerevisiae cytosolic aspartate aminotransferase.
The crystal structure of Saccharomyces cerevisiae cytoplasmic aspartate aminotransferase (EC 2.6.1.1) has been determined to 2.05 A resolution in the presence of the cofactor pyridoxal-5'-phosphate and the competitive inhibitor maleate. The structure was solved by the method of molecular replacement. The final value of the crystallographic R-factor after refinement was 23.1% with good geometry of the final model. The yeast cytoplasmic enzyme is a homodimer with two identical active sites containing residues from each subunit. It is found in the "closed" conformation with a bound maleate inhibitor in each active site. It shares the same three-dimensional fold and active site residues as the aspartate aminotransferases from Escherichia coli, chicken cytoplasm, and chicken mitochondria, although it shares less than 50% sequence identity with any of them. The availability of four similar enzyme structures from distant regions of the evolutionary tree provides a measure of tolerated changes that can arise during millions of years of evolution.
Jeffery
C J
CJ
Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02254-9110, USA.
Barry
T
T
Doonan
S
S
Petsko
G A
GA
Ringe
D
D
D000818:Animals; D001219:Aspartate Aminotransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000201:enzymology; D004271:DNA, Fungal / Q000737:chemistry; D019281:Dimerization; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D011732:Pyridoxal Phosphate / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D017385:Sequence Homology
D004271:DNA, Fungal; D011732:Pyridoxal Phosphate; D001219:Aspartate Aminotransferases