1nr1: Difference between revisions

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-[[Image:1nr1.gif|left|200px]]<br />
-<applet load="1nr1" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1nr1, resolution 3.30&Aring;" />
-'''Crystal structure of the R463A mutant of human Glutamate dehydrogenase'''<br />
-==Overview==
+==Crystal structure of the R463A mutant of human Glutamate dehydrogenase==
-Glutamate dehydrogenase (GDH) is found in all organisms and catalyzes the, reversible oxidative deamination of L-glutamate to 2-oxoglutarate. Unlike, GDH from bacteria, mammalian GDH exhibits negative cooperativity with, respect to coenzyme, activation by ADP, and inhibition by GTP. Presented, here are the structures of apo bovine GDH, bovine GDH complexed with ADP, and the R463A mutant form of human GDH (huGDH) that is insensitive to ADP, activation. In the absence of active site ligands, the catalytic cleft is, in the open conformation, and the hexamers form long polymers in the, crystal cell with more interactions than found in the abortive complex, crystals. This is consistent with the fact that ADP promotes aggregation, in solution. ADP is shown to bind to the second, inhibitory, NADH site yet, causes activation. The beta-phosphates of the bound ADP interact with R459, (R463 in huGDH) on the pivot helix. The structure of the ADP-resistant, R463A mutant of human GDH is identical to native GDH with the exception of, the truncated side chain on the pivot helix. Together, these results, strongly suggest that ADP activates by facilitating the opening of the, catalytic cleft. From alignment of GDH from various sources, it is likely, that the antenna evolved in the protista prior to the formation of purine, regulatory sites. This suggests that there was some selective advantage of, the antenna itself and that animals evolved new functions for GDH through, the addition of allosteric regulation.
+<StructureSection load='1nr1' size='340' side='right'caption='[[1nr1]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1nr1]] is a 6 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=1NR1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NR1 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]] 3.3&#8491;</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=1nr1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nr1 OCA], [https://pdbe.org/1nr1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nr1 RCSB], [https://www.ebi.ac.uk/pdbsum/1nr1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nr1 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/DHE3_HUMAN DHE3_HUMAN] Defects in GLUD1 are the cause of familial hyperinsulinemic hypoglycemia type 6 (HHF6) [MIM:[https://omim.org/entry/606762 606762]; also known as hyperinsulinism-hyperammonemia syndrome (HHS). Familial hyperinsulinemic hypoglycemia [MIM:[https://omim.org/entry/256450 256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. In HHF6 elevated oxidation rate of glutamate to alpha-ketoglutarate stimulates insulin secretion in the pancreatic beta cells, while they impair detoxification of ammonium in the liver.<ref>PMID:9571255</ref> <ref>PMID:10636977</ref> <ref>PMID:11214910</ref> <ref>PMID:11297618</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/DHE3_HUMAN DHE3_HUMAN] May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity).
+== 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/nr/1nr1_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=1nr1 ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-Known diseases associated with this structure: Hyperinsulinism-hyperammonemia syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138130 138130]]
+*[[Glutamate dehydrogenase 3D structures|Glutamate dehydrogenase 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-NR1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Glutamate_dehydrogenase_(NAD(P)(+)) Glutamate dehydrogenase (NAD(P)(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.1.3 1.4.1.3] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NR1 OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Structural studies on ADP activation of mammalian glutamate dehydrogenase and the evolution of regulation., Banerjee S, Schmidt T, Fang J, Stanley CA, Smith TJ, Biochemistry. 2003 Apr 1;42(12):3446-56. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12653548 12653548]
-[[Category: Glutamate dehydrogenase (NAD(P)(+))]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Banerjee, S.]]
+[[Category: Banerjee S]]
-[[Category: Fang, J]]
+[[Category: Fang J]]
-[[Category: Schmidt, T.]]
+[[Category: Schmidt T]]
-[[Category: Smith, T.J.]]
+[[Category: Smith TJ]]
-[[Category: Stanley, C.A.]]
+[[Category: Stanley CA]]
-[[Category: glutamate dehydrogenase]]
-[[Category: hexamer]]
-[[Category: regulation]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:24:12 2007''