Structural highlights
6g7o is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
|
Ligands: | , , , , , |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[ACER3_HUMAN] Alkaline ceramidase 3 deficiency.
Function
[ACER3_HUMAN] Hydrolyzes only phytoceramide into phytosphingosine and free fatty acid. Does not have reverse activity.
Publication Abstract from PubMed
Alkaline ceramidases (ACERs) are a class of poorly understood transmembrane enzymes controlling the homeostasis of ceramides. They are implicated in human pathophysiology, including progressive leukodystrophy, colon cancer as well as acute myeloid leukemia. We report here the crystal structure of the human ACER type 3 (ACER3). Together with computational studies, the structure reveals that ACER3 is an intramembrane enzyme with a seven transmembrane domain architecture and a catalytic Zn(2+) binding site in its core, similar to adiponectin receptors. Interestingly, we uncover a Ca(2+) binding site physically and functionally connected to the Zn(2+) providing a structural explanation for the known regulatory role of Ca(2+) on ACER3 enzymatic activity and for the loss of function in E33G-ACER3 mutant found in leukodystrophic patients.
Structure of a human intramembrane ceramidase explains enzymatic dysfunction found in leukodystrophy.,Vasiliauskaite-Brooks I, Healey RD, Rochaix P, Saint-Paul J, Sounier R, Grison C, Waltrich-Augusto T, Fortier M, Hoh F, Saied EM, Arenz C, Basu S, Leyrat C, Granier S Nat Commun. 2018 Dec 21;9(1):5437. doi: 10.1038/s41467-018-07864-w. PMID:30575723[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Vasiliauskaite-Brooks I, Healey RD, Rochaix P, Saint-Paul J, Sounier R, Grison C, Waltrich-Augusto T, Fortier M, Hoh F, Saied EM, Arenz C, Basu S, Leyrat C, Granier S. Structure of a human intramembrane ceramidase explains enzymatic dysfunction found in leukodystrophy. Nat Commun. 2018 Dec 21;9(1):5437. doi: 10.1038/s41467-018-07864-w. PMID:30575723 doi:http://dx.doi.org/10.1038/s41467-018-07864-w