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1u8f

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(New page: 200px<br /> <applet load="1u8f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u8f, resolution 1.75&Aring;" /> '''Crystal Structure O...)
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[[Image:1u8f.gif|left|200px]]<br />
 
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<applet load="1u8f" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1u8f, resolution 1.75&Aring;" />
 
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'''Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution'''<br />
 
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==Overview==
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==Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution==
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GAPDH (D-glyceraldehyde-3-phosphate dehydrogenase) is a multifunctional, protein that is a target for the design of antitrypanosomatid and, anti-apoptosis drugs. Here, the first high-resolution (1.75 Angstroms), structure of a human GAPDH is reported. The structure shows that the, intersubunit selectivity cleft that has been leveraged in the design of, antitrypanosomatid compounds is closed in human GAPDH. Modeling of an, anti-trypanosomatid GAPDH inhibitor in the human GAPDH active site, provides insights into the basis for the observed selectivity of this, class of inhibitor. Moreover, the high-resolution data reveal a new, feature of the cleft: water-mediated intersubunit hydrogen bonds that, assist closure of the cleft in the human enzyme. The structure is used in, a computational ligand-docking study of the small-molecule compound, CGP-3466, which inhibits apoptosis by preventing nuclear accumulation of, GAPDH. Plausible binding sites are identified in the adenosine pocket of, the NAD(+)-binding site and in a hydrophobic channel located in the center, of the tetramer near the intersection of the three molecular twofold axes., The structure is also used to build a qualitative model of the complex, between GAPDH and the E3 ubiquitin ligase Siah1. The model suggests that, the convex surface near GAPDH Lys227 interacts with a large shallow groove, of the Siah1 dimer. These results are discussed in the context of the, recently discovered NO-S-nitrosylation-GAPDH-Siah1 apoptosis cascade.
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<StructureSection load='1u8f' size='340' side='right'caption='[[1u8f]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1u8f]] is a 4 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=1U8F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U8F FirstGlance]. <br>
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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]] 1.75&#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=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
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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=1u8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u8f OCA], [https://pdbe.org/1u8f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u8f RCSB], [https://www.ebi.ac.uk/pdbsum/1u8f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u8f ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/G3P_HUMAN G3P_HUMAN] Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.<ref>PMID:3170585</ref> <ref>PMID:11724794</ref> <ref>PMID:23071094</ref>
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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/u8/1u8f_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=1u8f ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1U8F 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 NAD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glyceraldehyde-3-phosphate_dehydrogenase_(phosphorylating) Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.12 1.2.1.12] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1U8F OCA].
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*[[Glyceraldehyde-3-phosphate dehydrogenase 3D structures|Glyceraldehyde-3-phosphate dehydrogenase 3D structures]]
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== References ==
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==Reference==
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<references/>
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High-resolution structure of human D-glyceraldehyde-3-phosphate dehydrogenase., Jenkins JL, Tanner JJ, Acta Crystallogr D Biol Crystallogr. 2006 Mar;62(Pt 3):290-301. Epub 2006, Feb 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16510976 16510976]
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__TOC__
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[[Category: Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)]]
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Jenkins, J.L.]]
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[[Category: Jenkins JL]]
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[[Category: Tanner, J.J.]]
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[[Category: Tanner JJ]]
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[[Category: NAD]]
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[[Category: dehydrogenase]]
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[[Category: gapd]]
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[[Category: gapdh]]
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[[Category: mammalian gapdh]]
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[[Category: oxidoreductase]]
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[[Category: rossmann fold]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:32:42 2007''
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Current revision

Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution

PDB ID 1u8f

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