6G7O

Crystal structure of human alkaline ceramidase 3 (ACER3) at 2.7 Angstrom resolution

Summary for 6G7O

• Entry DOI: 10.2210/pdb6g7o/pdb
• Descriptor: Alkaline ceramidase 3,Soluble cytochrome b562, ZINC ION, SULFATE ION, ... (8 entities in total)
• Functional Keywords: hydrolase, 7tm, zinc binding protein, calcium-binding protein, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 41647.04

Authors

Leyrat, C.,Vasiliauskaite-Brooks, I.,Healey, R.D.,Sounier, R.,Grison, C.,Hoh, F.,Basu, S.,Granier, S. (deposition date: 2018-04-06, release date: 2019-01-02, Last modification date: 2024-11-06)

Primary citation

Vasiliauskaite-Brooks, I.,Healey, R.D.,Rochaix, P.,Saint-Paul, J.,Sounier, R.,Grison, C.,Waltrich-Augusto, T.,Fortier, M.,Hoh, F.,Saied, E.M.,Arenz, C.,Basu, S.,Leyrat, C.,Granier, S.
Structure of a human intramembrane ceramidase explains enzymatic dysfunction found in leukodystrophy.
Nat Commun, 9:5437-5437, 2018

PubMed Abstract: 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 binding site in its core, similar to adiponectin receptors. Interestingly, we uncover a Ca binding site physically and functionally connected to the Zn providing a structural explanation for the known regulatory role of Ca on ACER3 enzymatic activity and for the loss of function in E33G-ACER3 mutant found in leukodystrophic patients.

PubMed: 30575723
DOI: 10.1038/s41467-018-07864-w

Experimental method

X-RAY DIFFRACTION (2.7 Å)