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1.
J Biol Chem ; 295(40): 13914-13926, 2020 10 02.
Article in English | MEDLINE | ID: mdl-32796031

ABSTRACT

Aldehyde dehydrogenases are versatile enzymes that serve a range of biochemical functions. Although traditionally considered metabolic housekeeping enzymes because of their ability to detoxify reactive aldehydes, like those generated from lipid peroxidation damage, the contributions of these enzymes to other biological processes are widespread. For example, the plant pathogen Pseudomonas syringae strain PtoDC3000 uses an indole-3-acetaldehyde dehydrogenase to synthesize the phytohormone indole-3-acetic acid to elude host responses. Here we investigate the biochemical function of AldC from PtoDC3000. Analysis of the substrate profile of AldC suggests that this enzyme functions as a long-chain aliphatic aldehyde dehydrogenase. The 2.5 Å resolution X-ray crystal of the AldC C291A mutant in a dead-end complex with octanal and NAD+ reveals an apolar binding site primed for aliphatic aldehyde substrate recognition. Functional characterization of site-directed mutants targeting the substrate- and NAD(H)-binding sites identifies key residues in the active site for ligand interactions, including those in the "aromatic box" that define the aldehyde-binding site. Overall, this study provides molecular insight for understanding the evolution of the prokaryotic aldehyde dehydrogenase superfamily and their diversity of function.


Subject(s)
Aldehyde Dehydrogenase/chemistry , Bacterial Proteins/chemistry , Plant Diseases/microbiology , Pseudomonas syringae/enzymology , Aldehyde Dehydrogenase/genetics , Bacterial Proteins/genetics , Crystallography, X-Ray , Pseudomonas syringae/genetics
2.
Future Med Chem ; 3(7): 881-6, 2011 May.
Article in English | MEDLINE | ID: mdl-21644833

ABSTRACT

Products for animal health commercialization follow a structured progression from initial concept through to regulatory approval. Typically, products are developed for use in either food animals or companion animals. These can be for the intention of disease intervention, productivity enhancement or improvement in a quality of life capacity. The animal health industry is a regulated industry, meaning that a government agency is responsible for oversight of products, both pre- and post-approval. There are three primary US government agencies that ensure quality, safety and effectiveness for the approval of new products and post-marketing compliance.


Subject(s)
Drug Approval/legislation & jurisprudence , Drug Industry , Veterinary Drugs/pharmacology , Animal Welfare/economics , Animals , Government Regulation
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