A new branch in the family: structure of aspartate-beta-semialdehyde dehydrogenase from Methanococcus jannaschii.
The structure of aspartate-beta-semialdehyde dehydrogenase (ASADH) from Methanococcus jannaschii has been determined to 2.3 angstroms resolution using multiwavelength anomalous diffraction (MAD) phasing of a selenomethionine-substituted derivative to define a new branch in the family of ASADHs. This new structure has a similar overall fold and domain organization despite less than 10% conserved sequence identity with the bacterial enzymes. However, the entire repertoire of functionally important active site amino acid residues is conserved, suggesting an identical catalytic mechanism but with lower catalytic efficiency. A new coenzyme-binding conformation and dual NAD/NADP coenzyme specificity further distinguish this archaeal branch from the bacterial ASADHs. Several structural differences are proposed to account for the dramatically enhanced thermostability of this archaeal enzyme. Finally, the intersubunit communication channel connecting the active sites in the bacterial enzyme dimer has been disrupted in the archaeal ASADHs by amino acid changes that likely prevent the alternating sites reactivity previously proposed for the bacterial ASADHs.
Faehnle
Christopher R
CR
Department of Chemistry, University of Toledo, 2801 W. Bancroft St., Toledo, OH 43606, USA.
Ohren
Jeffrey F
JF
Viola
Ronald E
RE
D019843:Archaeal Proteins / Q000737:chemistry; D001223:Aspartate-Semialdehyde Dehydrogenase / Q000737:chemistry*; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004795:Enzyme Stability; D017017:Methanococcus / Q000201:enzymology*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D012645:Selenomethionine; D016415:Sequence Alignment
D019843:Archaeal Proteins; D021122:Protein Subunits; D012645:Selenomethionine; D001223:Aspartate-Semialdehyde Dehydrogenase