1sd2

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{{STRUCTURE_1sd2| PDB=1sd2 | SCENE= }}
 
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===STRUCTURE OF HUMAN 5'-DEOXY-5'-METHYLTHIOADENOSINE PHOSPHORYLASE COMPLEXED WITH 5'-METHYLTHIOTUBERCIDIN===
 
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{{ABSTRACT_PUBMED_15122881}}
 
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==Disease==
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==STRUCTURE OF HUMAN 5'-DEOXY-5'-METHYLTHIOADENOSINE PHOSPHORYLASE COMPLEXED WITH 5'-METHYLTHIOTUBERCIDIN==
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[[http://www.uniprot.org/uniprot/MTAP_HUMAN MTAP_HUMAN]] Defects in MTAP are the cause of diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMSMFH) [MIM:[http://omim.org/entry/112250 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).<ref>PMID:22464254</ref> 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]
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<StructureSection load='1sd2' size='340' side='right'caption='[[1sd2]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1sd2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SD2 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTH:2-(4-AMINO-PYRROLO[2,3-D]PYRIMIDIN-7-YL)-5-METHYLSULFANYLMETHYL-TETRAHYDRO-FURAN-3,4-DIOL'>MTH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1sd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sd2 OCA], [https://pdbe.org/1sd2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sd2 RCSB], [https://www.ebi.ac.uk/pdbsum/1sd2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sd2 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/MTAP_HUMAN MTAP_HUMAN] Defects in MTAP are the cause of diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMSMFH) [MIM:[https://omim.org/entry/112250 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).<ref>PMID:22464254</ref> 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]
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== Function ==
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[https://www.uniprot.org/uniprot/MTAP_HUMAN MTAP_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.<ref>PMID:3091600</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sd/1sd2_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1sd2 ConSurf].
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<div style="clear:both"></div>
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==Function==
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==See Also==
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[[http://www.uniprot.org/uniprot/MTAP_HUMAN MTAP_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.<ref>PMID:3091600</ref>
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*[[5'-deoxy-5'-methylthioadenosine phosphorylase 3D structures|5'-deoxy-5'-methylthioadenosine phosphorylase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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[[1sd2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SD2 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:015122881</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: S-methyl-5'-thioadenosine phosphorylase]]
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[[Category: Large Structures]]
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[[Category: Cornell, K A.]]
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[[Category: Cornell KA]]
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[[Category: Ealick, S E.]]
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[[Category: Ealick SE]]
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[[Category: Howell, P L.]]
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[[Category: Howell PL]]
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[[Category: Lee, J E.]]
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[[Category: Lee JE]]
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[[Category: Riscoe, M K.]]
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[[Category: Riscoe MK]]
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[[Category: Settembre, E C.]]
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[[Category: Settembre EC]]
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[[Category: Sufrin, J R.]]
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[[Category: Sufrin JR]]
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[[Category: 5'-methylthiotubercidin]]
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[[Category: Methylthioadenosine phosphorylase]]
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[[Category: Mtt]]
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[[Category: Purine nucleoside phosphorylase]]
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[[Category: Purine salvage]]
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[[Category: Sulfate]]
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[[Category: Transferase]]
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Current revision

STRUCTURE OF HUMAN 5'-DEOXY-5'-METHYLTHIOADENOSINE PHOSPHORYLASE COMPLEXED WITH 5'-METHYLTHIOTUBERCIDIN

PDB ID 1sd2

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