4NPI

1.94 Angstroms X-ray crystal structure of NAD- and intermediate- bound alpha-aminomuconate-epsilon-semialdehyde dehydrogenase from Pseudomonas fluorescens

Summary for 4NPI

• Entry DOI: 10.2210/pdb4npi/pdb
• Descriptor: 2-aminomuconate 6-semialdehyde dehydrogenase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, SODIUM ION, ... (5 entities in total)
• Functional Keywords: aldh, dehydrogenase, nad+, oxidoreductase
• Biological source: Pseudomonas fluorescens
• Total number of polymer chains: 4
• Total formula weight: 211796.44

Authors

Huo, L.,Davis, I.,Liu, F.,Iwaki, H.,Hasegawa, Y.,Liu, A. (deposition date: 2013-11-21, release date: 2014-12-24, Last modification date: 2023-09-20)

Primary citation

Huo, L.,Davis, I.,Liu, F.,Andi, B.,Esaki, S.,Iwaki, H.,Hasegawa, Y.,Orville, A.M.,Liu, A.
Crystallographic and spectroscopic snapshots reveal a dehydrogenase in action.
Nat Commun, 6:5935-5935, 2015

PubMed Abstract: 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.

PubMed: 25565451
DOI: 10.1038/ncomms6935

Experimental method

X-RAY DIFFRACTION (1.94 Å)