http://purl.uniprot.org/citations/35931745 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/35931745 | http://www.w3.org/2000/01/rdf-schema#comment | "Human spermine oxidase (hSMOX) plays a central role in polyamine catabolism. Due to its association with several pathological processes, including inflammation and cancer, hSMOX has garnered interest as a possible therapeutic target. Therefore, determination of the structure of hSMOX is an important step to enable drug discovery and validate hSMOX as a drug target. Using insights from hydrogen/deuterium exchange mass spectrometry (HDX-MS), we engineered a hSMOX construct to obtain the first crystal structure of hSMOX bound to the known polyamine oxidase inhibitor MDL72527 at 2.4 Å resolution. While the overall fold of hSMOX is similar to its homolog, murine N1-acetylpolyamine oxidase (mPAOX), the two structures contain significant differences, notably in their substrate-binding domains and active site pockets. Subsequently, we employed a sensitive biochemical assay to conduct a high-throughput screen that identified a potent and selective hSMOX inhibitor, JNJ-1289. The co-crystal structure of hSMOX with JNJ-1289 was determined at 2.1 Å resolution, revealing that JNJ-1289 binds to an allosteric site, providing JNJ-1289 with a high degree of selectivity towards hSMOX. These results provide crucial insights into understanding the substrate specificity and enzymatic mechanism of hSMOX, and for the design of highly selective inhibitors."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.org/dc/terms/identifier | "doi:10.1038/s42003-022-03735-9"xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Diaz E."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Fang L."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Kirkpatrick R."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Tepper A.W.J.W."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Carbajo R.J."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Shaffer P.L."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Adhikary S."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Riley D."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Thomsen M."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Buyck C."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Fahmy S."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Impagliazzo A."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Krosky D."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Kalin J.H."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Klaren V.N.A."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Lamenca C.M."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Llaveria J."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/author | "Ortiz-Meoz R."xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/name | "Commun Biol"xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/pages | "787"xsd:string |
http://purl.uniprot.org/citations/35931745 | http://purl.uniprot.org/core/title | "Structure of human spermine oxidase in complex with a highly selective allosteric inhibitor."xsd:string |