Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli, a key enzyme in the aspartate family of amino acid biosynthesis. Academic Article uri icon

Overview

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.

publication date

  • June 18, 1999

Research

keywords

  • Aspartate-Semialdehyde Dehydrogenase
  • Aspartic Acid
  • Escherichia coli

Identity

Scopus Document Identifier

  • 0033047006

Digital Object Identifier (DOI)

  • 10.1006/jmbi.1999.2828

PubMed ID

  • 10369777

Additional Document Info

volume

  • 289

issue

  • 4