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'''Unreleased structure'''


The entry 5tc7 is ON HOLD until Paper Publication
==Crystal structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase in complex with 5'-methylthiotubercidin at 1.75 angstrom==
<StructureSection load='5tc7' size='340' side='right'caption='[[5tc7]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5tc7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TC7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TC7 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ozc|3ozc]], [[3ozd|3ozd]], [[3oze|3oze]], [[1k27|1k27]], [[5tc8|5tc8]], [[5tc6|5tc6]], [[5tc5|5tc5]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MTAP, MSAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/S-methyl-5'-thioadenosine_phosphorylase S-methyl-5'-thioadenosine phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.28 2.4.2.28] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tc7 OCA], [http://pdbe.org/5tc7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tc7 RCSB], [http://www.ebi.ac.uk/pdbsum/5tc7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tc7 ProSAT]</span></td></tr>
</table>
== Disease ==
[[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]
== Function ==
[[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>  


Authors: Cameron, S.A., Firestone, R.S., Schramm, V.L., Almo, S.C.
==See Also==
 
*[[5'-deoxy-5'-methylthioadenosine phosphorylase 3D structures|5'-deoxy-5'-methylthioadenosine phosphorylase 3D structures]]
Description: Crystal structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase in complex with 5'-methylthiotubercidin at 1.75 angstrom
== References ==
[[Category: Unreleased Structures]]
<references/>
[[Category: Almo, S.C]]
__TOC__
[[Category: Schramm, V.L]]
</StructureSection>
[[Category: Cameron, S.A]]
[[Category: Human]]
[[Category: Firestone, R.S]]
[[Category: Large Structures]]
[[Category: S-methyl-5'-thioadenosine phosphorylase]]
[[Category: Almo, S C]]
[[Category: Cameron, S A]]
[[Category: Firestone, R S]]
[[Category: Schramm, V L]]
[[Category: Inhibitor]]
[[Category: Phosphorylase]]
[[Category: Transferase-transferase inhibitor complex]]

Revision as of 12:23, 4 December 2019

Crystal structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase in complex with 5'-methylthiotubercidin at 1.75 angstromCrystal structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase in complex with 5'-methylthiotubercidin at 1.75 angstrom

Structural highlights

5tc7 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, ,
Gene:MTAP, MSAP (HUMAN)
Activity:S-methyl-5'-thioadenosine phosphorylase, with EC number 2.4.2.28
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MTAP_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]

Function

[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.[2]

See Also

References

  1. ↑ Camacho-Vanegas O, Camacho SC, Till J, Miranda-Lorenzo I, Terzo E, Ramirez MC, Schramm V, Cordovano G, Watts G, Mehta S, Kimonis V, Hoch B, Philibert KD, Raabe CA, Bishop DF, Glucksman MJ, Martignetti JA. Primate genome gain and loss: a bone dysplasia, muscular dystrophy, and bone cancer syndrome resulting from mutated retroviral-derived MTAP transcripts. Am J Hum Genet. 2012 Apr 6;90(4):614-27. doi: 10.1016/j.ajhg.2012.02.024. Epub, 2012 Mar 29. PMID:22464254 doi:10.1016/j.ajhg.2012.02.024
  2. ↑ Della Ragione F, Carteni-Farina M, Gragnaniello V, Schettino MI, Zappia V. Purification and characterization of 5'-deoxy-5'-methylthioadenosine phosphorylase from human placenta. J Biol Chem. 1986 Sep 15;261(26):12324-9. PMID:3091600

5tc7, resolution 1.75Å

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