1nr1: Difference between revisions

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<StructureSection load='1nr1' size='340' side='right'caption='[[1nr1]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
<StructureSection load='1nr1' size='340' side='right'caption='[[1nr1]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1nr1]] is a 6 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=1NR1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NR1 FirstGlance]. <br>
<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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1l1f|1l1f]], [[1nqt|1nqt]], [[1nr7|1nr7]]</div></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]] 3.3&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glutamate_dehydrogenase_(NAD(P)(+)) Glutamate dehydrogenase (NAD(P)(+))], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.1.3 1.4.1.3] </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=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>
<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>
</table>
== Disease ==
== 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>
[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 ==
== 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).  
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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].
</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>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.
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:12653548<ref>PMID:12653548</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1nr1" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[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: Oxidoreductase]]
[[Category: Regulation]]

Latest revision as of 10:59, 14 February 2024

Crystal structure of the R463A mutant of human Glutamate dehydrogenaseCrystal structure of the R463A mutant of human Glutamate dehydrogenase

Structural highlights

1nr1 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.3Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

DHE3_HUMAN Defects in GLUD1 are the cause of familial hyperinsulinemic hypoglycemia type 6 (HHF6) [MIM:606762; also known as hyperinsulinism-hyperammonemia syndrome (HHS). Familial hyperinsulinemic hypoglycemia [MIM: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.[1] [2] [3] [4]

Function

DHE3_HUMAN May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Stanley CA, Lieu YK, Hsu BY, Burlina AB, Greenberg CR, Hopwood NJ, Perlman K, Rich BH, Zammarchi E, Poncz M. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med. 1998 May 7;338(19):1352-7. PMID:9571255
  2. ↑ Miki Y, Taki T, Ohura T, Kato H, Yanagisawa M, Hayashi Y. Novel missense mutations in the glutamate dehydrogenase gene in the congenital hyperinsulinism-hyperammonemia syndrome. J Pediatr. 2000 Jan;136(1):69-72. PMID:10636977
  3. ↑ Santer R, Kinner M, Passarge M, Superti-Furga A, Mayatepek E, Meissner T, Schneppenheim R, Schaub J. Novel missense mutations outside the allosteric domain of glutamate dehydrogenase are prevalent in European patients with the congenital hyperinsulinism-hyperammonemia syndrome. Hum Genet. 2001 Jan;108(1):66-71. PMID:11214910
  4. ↑ MacMullen C, Fang J, Hsu BY, Kelly A, de Lonlay-Debeney P, Saudubray JM, Ganguly A, Smith TJ, Stanley CA. Hyperinsulinism/hyperammonemia syndrome in children with regulatory mutations in the inhibitory guanosine triphosphate-binding domain of glutamate dehydrogenase. J Clin Endocrinol Metab. 2001 Apr;86(4):1782-7. PMID:11297618

1nr1, resolution 3.30Å

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