1cg6: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:1cg6.png|left|200px]]
-<!--
+==STRUCTURE OF HUMAN 5'-DEOXY-5'-METHYLTHIOADENOSINE PHOSPHORYLASE COMPLEXED WITH 5'-DEOXY-5'-METHYLTHIOADENOSINE AND SULFATE AT 1.7 A RESOLUTION==
-The line below this paragraph, containing "STRUCTURE_1cg6", creates the "Structure Box" on the page.
+<StructureSection load='1cg6' size='340' side='right'caption='[[1cg6]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1cg6]] 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=1CG6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CG6 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTA:5-DEOXY-5-METHYLTHIOADENOSINE'>MTA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_1cg6|  PDB=1cg6  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1cg6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cg6 OCA], [https://pdbe.org/1cg6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cg6 RCSB], [https://www.ebi.ac.uk/pdbsum/1cg6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cg6 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[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]
+== Function ==
+[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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cg/1cg6_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1cg6 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+BACKGROUND: 5'-Deoxy-5'-methylthioadenosine phosphorylase (MTAP) catalyzes the reversible phosphorolysis of 5'-deoxy-5'-methylthioadenosine (MTA) to adenine and 5-methylthio-D-ribose-1-phosphate. MTA is a by-product of polyamine biosynthesis, which is essential for cell growth and proliferation. This salvage reaction is the principle source of free adenine in human cells. Because of its importance in coupling the purine salvage pathway to polyamine biosynthesis MTAP is a potential chemotherapeutic target. RESULTS: We have determined the crystal structure of MTAP at 1.7 A resolution using multiwavelength anomalous diffraction phasing techniques. MTAP is a trimer comprised of three identical subunits. Each subunit consists of a single alpha/beta domain containing a central eight-stranded mixed beta sheet, a smaller five-stranded mixed beta sheet and six alpha helices. The native structure revealed the presence of an adenine molecule in the purine-binding site. The structure of MTAP with methylthioadenosine and sulfate ion soaked into the active site was also determined using diffraction data to 1.7 A resolution. CONCLUSIONS: The overall quaternary structure and subunit topology of MTAP are similar to mammalian purine nucleoside phosphorylase (PNP). The structures of the MTAP-ligand complexes provide a map of the active site and suggest possible roles for specific residues in substrate binding and catalysis. Residues accounting for the differences in substrate specificity between MTAP and PNP are also identified. Detailed information about the structure and chemical nature of the MTAP active site will aid in the rational design of inhibitors of this potential chemotherapeutic target. The MTAP structure represents the first structure of a mammalian PNP that is specific for 6-aminopurines.
-===STRUCTURE OF HUMAN 5'-DEOXY-5'-METHYLTHIOADENOSINE PHOSPHORYLASE COMPLEXED WITH 5'-DEOXY-5'-METHYLTHIOADENOSINE AND SULFATE AT 1.7 A RESOLUTION===
+The structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase at 1.7 A resolution provides insights into substrate binding and catalysis.,Appleby TC, Erion MD, Ealick SE Structure. 1999 Jun 15;7(6):629-41. PMID:10404592<ref>PMID:10404592</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1cg6" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_10404592}}, adds the Publication Abstract to the page
+*[[5'-deoxy-5'-methylthioadenosine phosphorylase|5'-deoxy-5'-methylthioadenosine phosphorylase]]
-(as it appears on PubMed at http://www.pubmed.gov), where 10404592 is the PubMed ID number.
+*[[5'-deoxy-5'-methylthioadenosine phosphorylase 3D structures|5'-deoxy-5'-methylthioadenosine phosphorylase 3D structures]]
--->
+== References ==
-{{ABSTRACT_PUBMED_10404592}}
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-CG6 is a [[Single protein]] structure of 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=1CG6 OCA].
-==Reference==
-The structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase at 1.7 A resolution provides insights into substrate binding and catalysis., Appleby TC, Erion MD, Ealick SE, Structure. 1999 Jun 15;7(6):629-41. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10404592 10404592]
 [[Category: Homo sapiens]]
-[[Category: S-methyl-5-thioadenosine phosphorylase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Appleby TC]]
-[[Category: Appleby, T C.]]
+[[Category: Ealick SE]]
-[[Category: Ealick, S E.]]
+[[Category: Erion MD]]
-[[Category: Erion, M D.]]
-[[Category: Methylthioadenosine]]
-[[Category: Methylthioadenosine phosphorylase]]
-[[Category: Purine nucleoside phosphorylase]]
-[[Category: Purine salvage]]
-[[Category: Sulfate]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 20:42:25 2008''