1iat: Difference between revisions

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-[[Image:1iat.gif|left|200px]]<br /><applet load="1iat" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1iat, resolution 1.62&Aring;" />
-'''CRYSTAL STRUCTURE OF HUMAN PHOSPHOGLUCOSE ISOMERASE/NEUROLEUKIN/AUTOCRINE MOTILITY FACTOR/MATURATION FACTOR'''<br />
-==Overview==
+==CRYSTAL STRUCTURE OF HUMAN PHOSPHOGLUCOSE ISOMERASE/NEUROLEUKIN/AUTOCRINE MOTILITY FACTOR/MATURATION FACTOR==
-Phosphoglucose isomerase (PGI) is a multifunctional protein, which, inside the cell, functions as a housekeeping enzyme of glycolysis and gluconeogenesis and, outside the cell, exerts wholly unrelated cytokine properties. We have determined the structure of human PGI to a resolution of 1.6 A using X-ray crystallography. The structure is highly similar to other PGIs, especially the architecture of the active site. Fortuitous binding of a sulphate molecule from the crystallisation solution has facilitated an accurate description of the substrate phosphate-binding site. Comparison with both native and inhibitor-bound rabbit PGI structures shows that two loops move closer to the active site upon binding inhibitor. Interestingly, the human structure most closely resembles the inhibitor-bound structure, suggesting that binding of the phosphate moiety of the substrate may trigger this conformational change. We suggest a new mechanism for catalysis that uses Glu357 as the base catalyst for the isomerase reaction rather than His388 as proposed previously. The human PGI structure has also provided a detailed framework with which to map mutations associated with non-spherocytic haemolytic anaemia.
+<StructureSection load='1iat' size='340' side='right'caption='[[1iat]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1iat]] 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=1IAT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IAT FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.62&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1iat FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iat OCA], [https://pdbe.org/1iat PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1iat RCSB], [https://www.ebi.ac.uk/pdbsum/1iat PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1iat ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/G6PI_HUMAN G6PI_HUMAN] Defects in GPI are the cause of hemolytic anemia non-spherocytic due to glucose phosphate isomerase deficiency (HA-GPID) [MIM:[https://omim.org/entry/613470 613470]. It is a form of anemia in which there is no abnormal hemoglobin or spherocytosis. It is caused by glucose phosphate isomerase deficiency. Severe GPI deficiency can be associated with hydrops fetalis, immediate neonatal death and neurological impairment.
+== Function ==
+[https://www.uniprot.org/uniprot/G6PI_HUMAN G6PI_HUMAN] Besides it's role as a glycolytic enzyme, mammalian GPI can function as a tumor-secreted cytokine and an angiogenic factor (AMF) that stimulates endothelial cell motility. GPI is also a neurotrophic factor (Neuroleukin) for spinal and sensory neurons.<ref>PMID:11004567</ref> <ref>PMID:11437381</ref> <ref>PMID:12163179</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/ia/1iat_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=1iat ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-Known diseases associated with this structure: Hemolytic anemia due to glucosephosphate isomerase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=172400 172400]], Hydrops fetalis, one form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=172400 172400]]
+*[[Phosphoglucose isomerase 3D structures|Phosphoglucose isomerase 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-IAT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=BME:'>BME</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glucose-6-phosphate_isomerase Glucose-6-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.9 5.3.1.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IAT OCA].
+__TOC__
+</StructureSection>
-==Reference==
-The crystal structure of human phosphoglucose isomerase at 1.6 A resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia., Read J, Pearce J, Li X, Muirhead H, Chirgwin J, Davies C, J Mol Biol. 2001 Jun 1;309(2):447-63. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11371164 11371164]
-[[Category: Glucose-6-phosphate isomerase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Chirgwin, J.]]
+[[Category: Chirgwin J]]
-[[Category: Davies, C.]]
+[[Category: Davies C]]
-[[Category: Li, X.]]
+[[Category: Li X]]
-[[Category: Muirhead, H.]]
+[[Category: Muirhead H]]
-[[Category: Pearce, J.]]
+[[Category: Pearce J]]
-[[Category: Read, J A.]]
+[[Category: Read JA]]
-[[Category: BME]]
-[[Category: SO4]]
-[[Category: glycolysis enzyme/neurotrophic growth factor/cytokine]]
-[[Category: isomerase]]
-[[Category: two alpha/beta domains]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:09:49 2008''