6rkf | pdb_00006rkf
Structure of human DASPO
Structural highlights
FunctionOXDD_HUMAN Selectively catalyzes the oxidative deamination of D-aspartate and its N-methylated derivative, N-methyl D-aspartate. Publication Abstract from PubMedd-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. Structure and kinetic properties of human d-aspartate oxidase, the enzyme-controlling d-aspartate levels in brain.,Molla G, Chaves-Sanjuan A, Savinelli A, Nardini M, Pollegioni L FASEB J. 2020 Jan;34(1):1182-1197. doi: 10.1096/fj.201901703R. Epub 2019 Nov 29. PMID:31914658[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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