6RKF

Structure of human DASPO

Summary for 6RKF

• Entry DOI: 10.2210/pdb6rkf/pdb
• Descriptor: D-aspartate oxidase, FLAVIN-ADENINE DINUCLEOTIDE, GLYCEROL, ... (6 entities in total)
• Functional Keywords: d-aspartate oxidase, d-aspartate, flavoprotein, oxidase, daspo, hdaspo, ddo, hddo oxidoreductase, fad
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 238106.49

Authors

Chaves-Sanjuan, A.,Nardini, M. (deposition date: 2019-04-30, release date: 2020-03-11, Last modification date: 2024-01-24)

Primary citation

Molla, G.,Chaves-Sanjuan, A.,Savinelli, A.,Nardini, M.,Pollegioni, L.
Structure and kinetic properties of human d-aspartate oxidase, the enzyme-controlling d-aspartate levels in brain.
Faseb J., 34:1182-1197, 2020

PubMed Abstract: d-Amino acids are the "wrong" enantiomers of amino acids as they are not used in proteins synthesis but evolved in selected functions. On this side, d-aspartate (d-Asp) plays several significant roles in mammals, especially as an agonist of N-methyl-d-aspartate receptors (NMDAR), and is involved in relevant diseases, such as schizophrenia and Alzheimer's disease. In vivo modulation of d-Asp levels represents an intriguing task to cope with such pathological states. As little is known about d-Asp synthesis, the only option for modulating the levels is via degradation, which is due to the flavoenzyme d-aspartate oxidase (DASPO). Here we present the first three-dimensional structure of a DASPO enzyme (from human) which belongs to the d-amino acid oxidase family. Notably, human DASPO differs from human d-amino acid oxidase (attributed to d-serine degradation, the main coagonist of NMDAR) showing peculiar structural features (a specific active site charge distribution), oligomeric state and kinetic mechanism, and a higher FAD affinity and activity. These results provide useful insights into the structure-function relationships of human DASPO: modulating its activity represents now a feasible novel therapeutic target.

PubMed: 31914658
DOI: 10.1096/fj.201901703R

Experimental method

X-RAY DIFFRACTION (3.219 Å)