1l1f: Difference between revisions

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-[[Image:1l1f.gif|left|200px]]<br />
-<applet load="1l1f" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1l1f, resolution 2.7&Aring;" />
-'''Structure of human glutamate dehydrogenase-apo form'''<br />
-==Overview==
+==Structure of human glutamate dehydrogenase-apo form==
-The structure of human glutamate dehydrogenase (GDH) has been determined, in the absence of active site and regulatory ligands. Compared to the, structures of bovine GDH that were complexed with coenzyme and substrate, the NAD binding domain is rotated away from the glutamate-binding domain., The electron density of this domain is more disordered the further it is, from the pivot helix. Mass spectrometry results suggest that this is, likely due to the apo form being more dynamic than the closed form. The, antenna undergoes significant conformational changes as the catalytic, cleft opens. The ascending helix in the antenna moves in a clockwise, manner and the helix in the descending strand contracts in a manner akin, to the relaxation of an extended spring. A number of spontaneous mutations, in this antenna region cause the hyperinsulinism/hyperammonemia syndrome, by decreasing GDH sensitivity to the inhibitor, GTP. Since these residues, do not directly contact the bound GTP, the conformational changes in the, antenna are apparently crucial to GTP inhibition. In the open, conformation, the GTP binding site is distorted such that it can no longer, bind GTP. In contrast, ADP binding benefits by the opening of the, catalytic cleft since R463 on the pivot helix is pushed into contact, distance with the beta-phosphate of ADP. These results support the, previous proposal that purines regulate GDH activity by altering the, dynamics of the NAD binding domain. Finally, a possible structural, mechanism for negative cooperativity is presented.
+<StructureSection load='1l1f' size='340' side='right'caption='[[1l1f]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1l1f]] 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=1L1F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L1F 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]] 2.7&#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=1l1f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l1f OCA], [https://pdbe.org/1l1f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l1f RCSB], [https://www.ebi.ac.uk/pdbsum/1l1f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l1f 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/l1/1l1f_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=1l1f 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/>
-L1F 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=1L1F OCA].
+__TOC__
+</StructureSection>
-==Reference==
-The structure of apo human glutamate dehydrogenase details subunit communication and allostery., Smith TJ, Schmidt T, Fang J, Wu J, Siuzdak G, Stanley CA, J Mol Biol. 2002 May 3;318(3):765-77. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12054821 12054821]
-[[Category: Glutamate dehydrogenase (NAD(P)(+))]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Fang, J.]]
+[[Category: Fang J]]
-[[Category: Schmidt, T.]]
+[[Category: Schmidt T]]
-[[Category: Siuzdak, G.]]
+[[Category: Siuzdak G]]
-[[Category: Smith, T.J.]]
+[[Category: Smith TJ]]
-[[Category: Stanley, C.A.]]
+[[Category: Stanley CA]]
-[[Category: Wu, J.]]
+[[Category: Wu J]]
-[[Category: allostery]]
-[[Category: negative cooperativity]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:56:19 2007''