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 {angstrom} resolution using multiwavelength anomalous diffraction (MAD) phasing of a selenomethionine-substituted derivative to define a new branch in the family of ASADHs. T...

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Bibliographic Details
Published in:Journal of molecular biology 2010-07, Vol.353 ((5) ; 2005)
Main Authors: Faehnle, Christopher R., Ohren, Jeffrey F., Viola, Ronald E.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
AMINO ACIDS
BASIC BIOLOGICAL SCIENCES
COENZYMES
COMMUNICATIONS
DIFFRACTION
DIMERS
EFFICIENCY
ENZYMES
OXIDOREDUCTASES
RESIDUES
RESOLUTION
SPECIFICITY
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Summary:The structure of aspartate-{beta}-semialdehyde dehydrogenase (ASADH) from Methanococcus jannaschii has been determined to 2.3 {angstrom} 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.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2005.09.027