4OUB: A 2.20 angstroms X-ray crystal structure of E268A 2-aminomucaonate 6-semialdehyde dehydrogenase catalytic intermediate from Pseudomonas fluorescens

Aldehydes are ubiquitous intermediates in metabolic pathways and their innate reactivity can often make them quite unstable. There are several aldehydic intermediates in the metabolic pathway for tryptophan degradation that can decay into neuroactive compounds that have been associated with numerous neurological diseases. An enzyme of this pathway, 2-aminomuconate-6-semialdehyde dehydrogenase, is responsible for 'disarming' the final aldehydic intermediate. Here we show the crystal structures of a bacterial analogue enzyme in five catalytically relevant forms: resting state, one binary and two ternary complexes, and a covalent, thioacyl intermediate. We also report the crystal structures of a tetrahedral, thiohemiacetal intermediate, a thioacyl intermediate and an NAD(+)-bound complex from an active site mutant. These covalent intermediates are characterized by single-crystal and solution-state electronic absorption spectroscopy. The crystal structures reveal that the substrate undergoes an E/Z isomerization at the enzyme active site before an sp(3)-to-sp(2) transition during enzyme-mediated oxidation.
PDB ID: 4OUBDownload
MMDB ID: 126377
PDB Deposition Date: 2014/2/15
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 2.19  Å
Source Organism:
Similar Structures:
Biological Unit for 4OUB: tetrameric; determined by author and by software (PISA)
Molecular Components in 4OUB
Label Count Molecule
Proteins (4 molecules)
2-aminomuconate 6-semialdehyde Dehydrogenase
Molecule annotation
Chemicals (12 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB