1k27 - Revision history

OCA at 08:49, 16 August 2023

OCA — Wed, 16 Aug 2023 08:49:28 GMT

←Older revision		Revision as of 08:49, 16 August 2023
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	<StructureSection load='1k27' size='340' side='right'caption='[[1k27]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='1k27' size='340' side='right'caption='[[1k27]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1k27]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K27 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1k27]] 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=1K27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K27 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTM:(3S,4R)-2-(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-5-[(METHYLSULFANYL)METHYL]PYRROLIDINE-3,4-DIOL'>MTM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.95Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/S-methyl-5'-thioadenosine_phosphorylase S-methyl-5'-thioadenosine phosphorylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.28 2.4.2.28] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTM:(3S,4R)-2-(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-5-[(METHYLSULFANYL)METHYL]PYRROLIDINE-3,4-DIOL'>MTM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k27 OCA], [https://pdbe.org/1k27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k27 RCSB], [https://www.ebi.ac.uk/pdbsum/1k27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k27 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k27 OCA], [https://pdbe.org/1k27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k27 RCSB], [https://www.ebi.ac.uk/pdbsum/1k27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k27 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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]	+	[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 ==		== 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>	+	[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 ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: S-methyl-5'-thioadenosine phosphorylase]]~~	+	[[Category: Almo SC]]
-	[[Category: Almo~~, S C~~]]	+	[[Category: Furneaux RH]]
-	[[Category: Furneaux~~, R H~~]]	+	[[Category: Schramm VL]]
-	[[Category: Schramm~~, V L~~]]	+	[[Category: Shi W]]
-	[[Category: Shi, W]]	+	[[Category: Singh V]]
-	[[Category: Singh, V]]	+	[[Category: Tyler PC]]
-	[[Category: Tyler~~, P C]]~~	+
-	~~[[Category: Methylthioadenosine phosphorylase]]~~	+
-	~~[[Category: Mtap]]~~	+
-	~~[[Category: Phosphate]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transition state analogue~~]]	+

OCA at 06:48, 11 August 2021

OCA — Wed, 11 Aug 2021 06:48:28 GMT

OCA at 09:32, 6 November 2019

OCA — Wed, 06 Nov 2019 09:32:19 GMT

←Older revision		Revision as of 09:32, 6 November 2019
Line 1:		Line 1:

	==Crystal Structure of 5'-Deoxy-5'-Methylthioadenosine Phosphorylase in Complex with a Transition State Analogue==		==Crystal Structure of 5'-Deoxy-5'-Methylthioadenosine Phosphorylase in Complex with a Transition State Analogue==
-	<StructureSection load='1k27' size='340' side='right' caption='[[1k27]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='1k27' size='340' side='right'caption='[[1k27]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1k27]] 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=1K27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1K27 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1k27]] 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=1K27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1K27 FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 1k27" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1k27" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[5'-deoxy-5'-methylthioadenosine phosphorylase 3D structures\|5'-deoxy-5'-methylthioadenosine phosphorylase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 36:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: S-methyl-5'-thioadenosine phosphorylase]]		[[Category: S-methyl-5'-thioadenosine phosphorylase]]
	[[Category: Almo, S C]]		[[Category: Almo, S C]]

OCA at 21:38, 24 January 2018

OCA — Wed, 24 Jan 2018 21:38:40 GMT

←Older revision		Revision as of 21:38, 24 January 2018
Line 1:		Line 1:
		+
	==Crystal Structure of 5'-Deoxy-5'-Methylthioadenosine Phosphorylase in Complex with a Transition State Analogue==		==Crystal Structure of 5'-Deoxy-5'-Methylthioadenosine Phosphorylase in Complex with a Transition State Analogue==
	<StructureSection load='1k27' size='340' side='right' caption='[[1k27]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='1k27' size='340' side='right' caption='[[1k27]], [[Resolution\|resolution]] 1.95Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTM:(3S,4R)-2-(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-5-[(METHYLSULFANYL)METHYL]PYRROLIDINE-3,4-DIOL'>MTM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTM:(3S,4R)-2-(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-5-[(METHYLSULFANYL)METHYL]PYRROLIDINE-3,4-DIOL'>MTM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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='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=1k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k27 OCA], [http://pdbe.org/1k27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1k27 RCSB], [http://www.ebi.ac.uk/pdbsum/1k27 PDBsum]</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=1k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k27 OCA], [http://pdbe.org/1k27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1k27 RCSB], [http://www.ebi.ac.uk/pdbsum/1k27 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1k27 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k2/1k27_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k2/1k27_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 30:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 1k27" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1k27" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[5'-deoxy-5'-methylthioadenosine phosphorylase\|5'-deoxy-5'-methylthioadenosine phosphorylase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:23, 9 February 2016

OCA — Tue, 09 Feb 2016 17:23:51 GMT

←Older revision		Revision as of 17:23, 9 February 2016
Line 19:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</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/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</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=1k27 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 00:28, 11 September 2015

OCA — Fri, 11 Sep 2015 00:28:53 GMT

←Older revision		Revision as of 00:28, 11 September 2015
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	<StructureSection load='1k27' size='340' side='right' caption='[[1k27]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='1k27' size='340' side='right' caption='[[1k27]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1k27]] 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=1K27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1K27 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1k27]] 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=1K27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1K27 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTM:(3S,4R)-2-(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-5-[(METHYLSULFANYL)METHYL]PYRROLIDINE-3,4-DIOL'>MTM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTM:(3S,4R)-2-(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-5-[(METHYLSULFANYL)METHYL]PYRROLIDINE-3,4-DIOL'>MTM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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='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=1k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k27 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1k27 RCSB], [http://www.ebi.ac.uk/pdbsum/1k27 PDBsum]</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=1k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k27 OCA], [http://pdbe.org/1k27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1k27 RCSB], [http://www.ebi.ac.uk/pdbsum/1k27 PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 1k27" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: S-methyl-5'-thioadenosine phosphorylase]]		[[Category: S-methyl-5'-thioadenosine phosphorylase]]
	[[Category: Almo, S C]]		[[Category: Almo, S C]]

OCA at 15:57, 5 January 2015

OCA — Mon, 05 Jan 2015 15:57:55 GMT

←Older revision		Revision as of 15:57, 5 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1k27]] 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=1K27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1K27 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1k27]] 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=1K27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1K27 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTM:(3S,4R)-2-(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-5-[(METHYLSULFANYL)METHYL]PYRROLIDINE-3,4-DIOL'>MTM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTM:(3S,4R)-2-(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-5-[(METHYLSULFANYL)METHYL]PYRROLIDINE-3,4-DIOL'>MTM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	<tr><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='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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k27 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1k27 RCSB], [http://www.ebi.ac.uk/pdbsum/1k27 PDBsum]</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=1k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k27 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1k27 RCSB], [http://www.ebi.ac.uk/pdbsum/1k27 PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== 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]		[[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]
Line 38:		Line 38:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: S-methyl-5'-thioadenosine phosphorylase]]		[[Category: S-methyl-5'-thioadenosine phosphorylase]]
-	[[Category: Almo, S C.]]	+	[[Category: Almo, S C]]
-	[[Category: Furneaux, R H.]]	+	[[Category: Furneaux, R H]]
-	[[Category: Schramm, V L.]]	+	[[Category: Schramm, V L]]
-	[[Category: Shi, W.]]	+	[[Category: Shi, W]]
-	[[Category: Singh, V.]]	+	[[Category: Singh, V]]
-	[[Category: Tyler, P C.]]	+	[[Category: Tyler, P C]]
	[[Category: Methylthioadenosine phosphorylase]]		[[Category: Methylthioadenosine phosphorylase]]
	[[Category: Mtap]]		[[Category: Mtap]]

OCA at 15:11, 29 September 2014

OCA — Mon, 29 Sep 2014 15:11:10 GMT

←Older revision		Revision as of 15:11, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1k27\| PDB=1k27 \| SCENE= }}~~	+	==Crystal Structure of 5'-Deoxy-5'-Methylthioadenosine Phosphorylase in Complex with a Transition State Analogue==
-	===Crystal Structure of 5'-Deoxy-5'-Methylthioadenosine Phosphorylase in Complex with a Transition State Analogue===	+	<StructureSection load='1k27' size='340' side='right' caption='[[1k27]], [[Resolution\|resolution]] 1.95Å' scene=''>
-	~~{{ABSTRACT_PUBMED_14705926}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1k27]] 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=1K27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1K27 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTM:(3S,4R)-2-(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-5-[(METHYLSULFANYL)METHYL]PYRROLIDINE-3,4-DIOL'>MTM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k27 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1k27 RCSB], [http://www.ebi.ac.uk/pdbsum/1k27 PDBsum]</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>
		+	== 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/k2/1k27_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/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Methythioadenosine phosphorylase (MTAP) functions solely in the polyamine pathway of mammals to remove the methylthioadenosine (MTA) product from both spermidine synthase (2.5.1.16) and spermine synthase (2.5.1.22). Inhibition of polyamine synthesis is a validated anticancer target. We designed and synthesized chemically stable analogues for the proposed transition state of human MTAP on the basis of the known ribooxacarbenium character at all reported N-ribosyltransferase transition states [Schramm, V. L. (2003) Acc. Chem. Res. 36, 588-596]. Methylthio-immucillin-A (MT-ImmA) is an iminoribitol tight-binding transition state analogue inhibitor with an equilibrium dissociation constant of 1.0 nM. The immucillins resemble the ribooxacarbenium ion transition states of N-ribosyltransferases and are tightly bound as the N4' cations. An ion pair formed between the iminoribitol cation and phosphate anion mimics the ribooxacarbenium cation-phosphate anion pair formed at the transition state and is confirmed in the crystal structure. The X-ray crystal structure of human MTAP with bound MT-Imm-A also reveals that the 5'-methylthio group lies in a flexible hydrophobic pocket. Substitution of the 5'-methylthio group with a 5'-phenylthio group gives an equilibrium binding constant of 1.0 nM. Methylthio-DADMe-immucillin-A is a pyrrolidine analogue of the transition state with a methylene bridge between the 9-deazaadenine group and the pyrrolidine ribooxacarbenium mimic. It is a slow-onset inhibitor with a dissociation constant of 86 pM. Improved binding energy with DADMe-immucillin-A suggests that the transition state is more closely matched by increasing the distance between leaving group and ribooxacarbenium mimics, consistent with a more dissociative transition state. Increasing the hydrophobic volume near the 5'-position at the catalytic site with 5'-phenylthio-DADMe-immucillin-A gave a dissociation constant of 172 pM, slightly weaker than the 5'-methylthio group. p-Cl-phenylthio-DADMe-immucillin-A binds with a dissociation constant of 10 pM (K(m)/K(i) value of 500000), the tightest binding inhibitor reported for MTAP. These slow-onset, tight-binding transition state analogue inhibitors are the most powerful reported for MTAP and have sufficient affinity to be useful in inhibiting the polyamine pathway.

-	~~==Disease==~~	+	Picomolar transition state analogue inhibitors of human 5'-methylthioadenosine phosphorylase and X-ray structure with MT-immucillin-A.,Singh V, Shi W, Evans GB, Tyler PC, Furneaux RH, Almo SC, Schramm VL Biochemistry. 2004 Jan 13;43(1):9-18. PMID:14705926<ref>PMID:14705926</ref>
-	~~[[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==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[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~~>	+	</div>

-	==~~About this Structure~~==	+	==See Also==
-	[[~~1k27~~]] 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=1K27 OCA].	+	*[[5'-deoxy-5'-methylthioadenosine phosphorylase\|5'-deoxy-5'-methylthioadenosine phosphorylase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:014705926</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: S-methyl-5'-thioadenosine phosphorylase]]		[[Category: S-methyl-5'-thioadenosine phosphorylase]]

OCA at 16:34, 24 March 2013

OCA — Sun, 24 Mar 2013 16:34:10 GMT

←Older revision		Revision as of 16:34, 24 March 2013
Line 1:		Line 1:
-	[[Image:1k27.png\|left\|200px]]
-
	{{STRUCTURE_1k27\| PDB=1k27 \| SCENE= }}		{{STRUCTURE_1k27\| PDB=1k27 \| SCENE= }}
-
	===Crystal Structure of 5'-Deoxy-5'-Methylthioadenosine Phosphorylase in Complex with a Transition State Analogue===		===Crystal Structure of 5'-Deoxy-5'-Methylthioadenosine Phosphorylase in Complex with a Transition State Analogue===
		+	{{ABSTRACT_PUBMED_14705926}}

-	~~{{ABSTRACT_PUBMED_14705926}}~~	+	==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>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:014705926</ref><references group="xtra"/>	+	<ref group="xtra">PMID:014705926</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: S-methyl-5'-thioadenosine phosphorylase]]		[[Category: S-methyl-5'-thioadenosine phosphorylase]]

OCA: Protected "1k27" [edit=sysop:move=sysop]

OCA — Wed, 05 Dec 2012 11:19:54 GMT

Protected "1k27" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:19, 5 December 2012

←Older revision		Revision as of 06:48, 11 August 2021
Line 3:		Line 3:
	<StructureSection load='1k27' size='340' side='right'caption='[[1k27]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='1k27' size='340' side='right'caption='[[1k27]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1k27]] 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=1K27 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1K27 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1k27]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K27 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTM:(3S,4R)-2-(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-5-[(METHYLSULFANYL)METHYL]PYRROLIDINE-3,4-DIOL'>MTM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTM:(3S,4R)-2-(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-5-[(METHYLSULFANYL)METHYL]PYRROLIDINE-3,4-DIOL'>MTM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/S-methyl-5'-thioadenosine_phosphorylase S-methyl-5'-thioadenosine phosphorylase], with EC number [https://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=1k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k27 OCA], [~~http~~://pdbe.org/1k27 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1k27 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1k27 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1k27 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k27 OCA], [https://pdbe.org/1k27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k27 RCSB], [https://www.ebi.ac.uk/pdbsum/1k27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k27 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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]	+	[[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 ==		== 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>	+	[[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 ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]