| http://purl.uniprot.org/citations/26190575 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26190575 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26190575 | http://www.w3.org/2000/01/rdf-schema#comment | "Neutral ceramidase (nCDase) catalyzes conversion of the apoptosis-associated lipid ceramide to sphingosine, the precursor for the proliferative factor sphingosine-1-phosphate. As an enzyme regulating the balance of ceramide and sphingosine-1-phosphate, nCDase is emerging as a therapeutic target for cancer. Here, we present the 2.6-Å crystal structure of human nCDase in complex with phosphate that reveals a striking, 20-Å deep, hydrophobic active site pocket stabilized by a eukaryotic-specific subdomain not present in bacterial ceramidases. Utilizing flexible ligand docking, we predict a likely binding mode for ceramide that superimposes closely with the crystallographically observed transition state analog phosphate. Our results suggest that nCDase uses a new catalytic strategy for Zn(2+)-dependent amidases, and generates ceramide specificity by sterically excluding sphingolipids with bulky headgroups and specifically recognizing the small hydroxyl head group of ceramide. Together, these data provide a foundation to aid drug development and establish common themes for how proteins recognize the bioactive lipid ceramide."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.str.2015.06.013"xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.str.2015.06.013"xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Hannun Y.A."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Hannun Y.A."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Obeid L.M."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Obeid L.M."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Airola M.V."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Airola M.V."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Allen W.J."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Allen W.J."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Pulkoski-Gross M.J."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Pulkoski-Gross M.J."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Rizzo R.C."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/author | "Rizzo R.C."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/name | "Structure"xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/name | "Structure"xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/pages | "1482-1491"xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/pages | "1482-1491"xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/title | "Structural Basis for Ceramide Recognition and Hydrolysis by Human Neutral Ceramidase."xsd:string |
| http://purl.uniprot.org/citations/26190575 | http://purl.uniprot.org/core/title | "Structural Basis for Ceramide Recognition and Hydrolysis by Human Neutral Ceramidase."xsd:string |