Publications by authors named "A L Peracchi"
The increasing availability of experimental and computational protein structures entices their use for function prediction. Here we develop an automated procedure to identify enzymes involved in metabolic reactions by assessing substrate conformations docked to a library of protein structures. By screening AlphaFold-modeled vitamin B6-dependent enzymes, we find that a metric based on catalytically favorable conformations at the enzyme active site performs best (AUROC Score=0.
View Article and Find Full Text PDFL-Ser supply in the central nervous system of mammals mostly relies on its endogenous biosynthesis by the phosphorylated pathway (PP). Defects in any of the three enzymes operating in the pathway result in a group of neurometabolic diseases collectively known as serine deficiency disorders (SDDs). Phosphoserine phosphatase (PSP) catalyzes the last, irreversible step of the PP.
View Article and Find Full Text PDFArticle Synopsis
- Phosphonates, which contain a direct carbon-phosphorus bond, are important sources of phosphorus in certain environments, with 2-aminoethylphosphonate (AEP) being the most common.
- Many bacteria can break down AEP using a specific pathway involving the enzyme PhnW; however, this process has limitations due to PhnW's inability to handle other related compounds like -methyl AEP (MAEP).
- The study introduces a new group of FAD-dependent oxidoreductases that can efficiently convert MAEP to phosphonoacetaldehyde (PAA), thus enhancing the degradation pathways of AEP and allowing some bacteria to generate PAA without relying on PhnW.
Article Synopsis
- * Microorganisms, particularly bacteria, have developed systems to utilize phosphonates as a resource in phosphate-limited environments, with these systems varying in specificity.
- * Research has focused on understanding the evolution, regulation, and mechanisms of microbial enzymes that degrade phosphonates, with at least three distinct enzymatic pathways identified for breaking down the C-P bond. *
In humans, the phosphorylated pathway (PP) converts the glycolytic intermediate D-3-phosphoglycerate (3-PG) into L-serine through the enzymes 3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase (PSAT) and phosphoserine phosphatase. From the pathogenic point of view, the PP in the brain is particularly relevant, as genetic defects of any of the three enzymes are associated with a group of neurometabolic disorders known as serine deficiency disorders (SDDs). We recombinantly expressed and characterized eight variants of PSAT associated with SDDs and two non-SDD associated variants.
View Article and Find Full Text PDF