5tc8
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Crystal structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase in complex with methylthio-DADMe-Immucillin-A
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Structural highlights
DiseaseMTAP_HUMAN Defects in MTAP are the cause of diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMSMFH) [MIM:112250. An autosomal dominant bone dysplasia characterized by pathologic fractures due to abnormal cortical growth and diaphyseal medullary stenosis. The fractures heal poorly, and there is progressive bowing of the lower extremities. Some patients show a limb-girdle myopathy, with muscle weakness and atrophy. Approximately 35% of affected individuals develop an aggressive form of bone sarcoma consistent with malignant fibrous histiocytoma or osteosarcoma. Note=DMSMFH causing mutations found in MTAP exon 9 result in exon skipping and dysregulated alternative splicing of all MTAP isoforms (PubMed:22464254).[1] Note=Loss of MTAP activity may play a role in human cancer. MTAP loss has been reported in a number of cancers, including osteosarcoma, malignant melanoma and gastric cancer.[HAMAP-Rule:MF_03155] FunctionMTAP_HUMAN Catalyzes the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates.[2] See AlsoReferences
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This page was last modified 12:57, 4 October 2023.