2r0n

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{{Seed}}
 
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[[Image:2r0n.png|left|200px]]
 
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==The effect of a Glu370Asp mutation in Glutaryl-CoA Dehydrogenase on Proton Transfer to the Dienolate Intermediate==
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The line below this paragraph, containing "STRUCTURE_2r0n", creates the "Structure Box" on the page.
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<StructureSection load='2r0n' size='340' side='right'caption='[[2r0n]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2r0n]] 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=2R0N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R0N FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=TGC:3-THIAGLUTARYL-COA'>TGC</scene></td></tr>
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{{STRUCTURE_2r0n| PDB=2r0n | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2r0n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r0n OCA], [https://pdbe.org/2r0n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r0n RCSB], [https://www.ebi.ac.uk/pdbsum/2r0n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r0n ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/GCDH_HUMAN GCDH_HUMAN] Defects in GCDH are the cause of glutaric aciduria type 1 (GA1) [MIM:[https://omim.org/entry/231670 231670]. GA1 is an autosomal recessive metabolic disorder characterized by progressive dystonia and athetosis due to gliosis and neuronal loss in the basal ganglia.<ref>PMID:18775954</ref> <ref>PMID:8541831</ref> <ref>PMID:9600243</ref> <ref>PMID:8900227</ref> <ref>PMID:8900228</ref> <ref>PMID:14707522</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/GCDH_HUMAN GCDH_HUMAN] Catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. Isoform Short is inactive.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r0/2r0n_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=2r0n ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We have determined steady-state rate constants and net rate constants for the chemical steps in the catalytic pathway catalyzed by the E370D mutant of glutaryl-CoA dehydrogenase and compared them with those of the wild-type dehydrogenase. We sought rationales for changes in these rate constants in the structure of the mutant cocrystallized with the alternate substrate, 4-nitrobutyric acid. Substitution of aspartate for E370, the catalytic base, results in a 24% decrease in the rate constant for proton abstraction at C-2 of 3-thiaglutaryl-CoA as the distance between C-2 of the ligand and the closest carboxyl oxygen at residue 370 increases from 2.9 A to 3.1 A. The net rate constant for flavin reduction due to hydride transfer from C-3 of the natural substrate, which includes proton abstraction at C-2, to N5 of the flavin decreases by 81% due to the mutation, although the distance increases only by 0.7 A. The intensities of charge-transfer bands associated with the enolate of 3-thiaglutaryl-CoA, the reductive half-reaction (reduced flavin with oxidized form of substrate), and the dienolate following decarboxylation are considerably diminished. Structural investigation suggests that the increased distance and the change in angle of the S-C1(=O)-C2 plane of the substrate with the isoalloxazine substantially alter rates of the reductive and oxidative half-reactions. This change in active site geometry also changes the position of protonation of the four carbon dienolate intermediate to produce kinetically favorable product, vinylacetyl-CoA, which is further isomerized to the thermodynamically stable normal product, crotonyl-CoA.
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===The effect of a Glu370Asp mutation in Glutaryl-CoA Dehydrogenase on Proton Transfer to the Dienolate Intermediate===
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The effect of a Glu370Asp mutation in glutaryl-CoA dehydrogenase on proton transfer to the dienolate intermediate.,Rao KS, Fu Z, Albro M, Narayanan B, Baddam S, Lee HJ, Kim JJ, Frerman FE Biochemistry. 2007 Dec 18;46(50):14468-77. Epub 2007 Nov 17. PMID:18020372<ref>PMID:18020372</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2r0n" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18020372}}, adds the Publication Abstract to the page
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*[[Acyl-CoA dehydrogenase 3D structures|Acyl-CoA dehydrogenase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 18020372 is the PubMed ID number.
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*[[Glutaryl-CoA dehydrogenase|Glutaryl-CoA dehydrogenase]]
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== References ==
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{{ABSTRACT_PUBMED_18020372}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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2R0N is a 1 chain structure of 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=2R0N OCA].
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==Reference==
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<ref group="xtra">PMID:18020372</ref><references group="xtra"/>
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[[Category: Glutaryl-CoA dehydrogenase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Albro, M.]]
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[[Category: Large Structures]]
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[[Category: Baddam, S.]]
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[[Category: Albro M]]
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[[Category: Frerman, F E.]]
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[[Category: Baddam S]]
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[[Category: Fu, Z.]]
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[[Category: Frerman FE]]
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[[Category: Kim, J J.]]
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[[Category: Fu Z]]
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[[Category: Lee, H J.]]
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[[Category: Kim JJ]]
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[[Category: Narayanan, B.]]
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[[Category: Lee HJ]]
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[[Category: Rao, K S.]]
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[[Category: Narayanan B]]
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[[Category: Alternative splicing]]
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[[Category: Rao KS]]
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[[Category: Disease mutation]]
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[[Category: Fad]]
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[[Category: Flavoprotein]]
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[[Category: Glutaryl-coa dehydrogenase]]
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[[Category: Isomerase]]
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[[Category: Mitochondrion]]
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[[Category: Oxidoreductase]]
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[[Category: Polymorphism]]
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[[Category: Transit peptide]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 21:52:48 2009''
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Current revision

The effect of a Glu370Asp mutation in Glutaryl-CoA Dehydrogenase on Proton Transfer to the Dienolate Intermediate

PDB ID 2r0n

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