Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli, a key enzyme in the aspartate family of amino acid biosynthesis.
J Mol Biol
; 289(4): 991-1002, 1999 Jun 18.
Article
em En
| MEDLINE
| ID: mdl-10369777
ABSTRACT
Aspartate beta-semialdehyde dehydrogenase (ASADH) lies at the first branch point in an essential aspartic biosynthetic pathway found in bacteria, fungi and the higher plants. Mutations in the asd gene encoding for ASADH that produce an inactive enzyme are lethal, which suggests that ASADH may be an effective target for antibacterial, herbicidal and fungicidal agents. We have solved the crystal structure of the Escherichia coli enzyme to 2.5 A resolution using single isomorphous replacement and 3-fold non-crystallographic symmetry. Each monomer has an N-terminal nucleotide-binding domain and a dimerisation domain. The presence of an essential cysteine locates the active site in a cleft between the two domains. The functional dimer has the appearance of a butterfly, with the NADP-binding domains forming the wings and the dimerisation domain forming the body.A histidine residue is identified as a likely acid/base catalyst in the enzymic reaction. Other amino acids implicated in the enzymic activity by mutagenesis are found in the active site region and define the substrate binding pocket.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aspartato-Semialdeído Desidrogenase
/
Ácido Aspártico
/
Escherichia coli
Idioma:
En
Revista:
J Mol Biol
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos