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1meo

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(New page: 200px<br /> <applet load="1meo" size="450" color="white" frame="true" align="right" spinBox="true" caption="1meo, resolution 1.72&Aring;" /> '''human glycinamide r...)
Current revision (07:43, 14 February 2024) (edit) (undo)
 
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[[Image:1meo.gif|left|200px]]<br />
 
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<applet load="1meo" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1meo, resolution 1.72&Aring;" />
 
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'''human glycinamide ribonucleotide Transformylase at pH 4.2'''<br />
 
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==Overview==
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==human glycinamide ribonucleotide Transformylase at pH 4.2==
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Glycinamide ribonucleotide transformylase (GAR Tfase) is a key, folate-dependent enzyme in the de novo purine biosynthesis pathway and, as, such, has been the target for antitumor drug design. Here, we describe the, crystal structures of the human GAR Tfase (purN) component of the human, trifunctional protein (purD-purM-purN) at various pH values and in complex, with its substrate. Human GAR Tfase exhibits pH-dependent enzyme activity, with its maximum around pH 7.5-8. Comparison of unliganded human GAR Tfase, structures at pH 4.2 and pH 8.5 reveals conformational differences in the, substrate binding loop, which at pH 4.2 occupies the binding cleft and, prohibits substrate binding, while at pH 8.5 is permissive for substrate, binding. The crystal structure of GAR Tfase with its natural substrate, beta-glycinamide ribonucleotide (beta-GAR), at pH 8.5 confirms this, conformational isomerism. Surprisingly, several important structural, differences are found between human GAR Tfase and previously reported E., coli GAR Tfase structures, which have been used as the primary template, for drug design studies. While the E. coli structure gave valuable, insights into the active site and formyl transfer mechanism, differences, in structure and inhibition between the bacterial and mammalian enzymes, suggest that the human GAR Tfase structure is now the appropriate template, for the design of anti-cancer agents.
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<StructureSection load='1meo' size='340' side='right'caption='[[1meo]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1meo]] 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=1MEO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MEO FirstGlance]. <br>
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1MEO 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 PO4 and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoribosylglycinamide_formyltransferase Phosphoribosylglycinamide formyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.2.2 2.1.2.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MEO OCA].
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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]] 1.72&#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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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==Reference==
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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=1meo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1meo OCA], [https://pdbe.org/1meo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1meo RCSB], [https://www.ebi.ac.uk/pdbsum/1meo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1meo ProSAT]</span></td></tr>
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Crystal structures of human GAR Tfase at low and high pH and with substrate beta-GAR., Zhang Y, Desharnais J, Greasley SE, Beardsley GP, Boger DL, Wilson IA, Biochemistry. 2002 Dec 3;41(48):14206-15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12450384 12450384]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PUR2_HUMAN PUR2_HUMAN]
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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/me/1meo_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=1meo ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Phosphoribosylglycinamide formyltransferase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Beardsley GP]]
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[[Category: Beardsley, G.P.]]
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[[Category: Boger DL]]
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[[Category: Boger, D.L.]]
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[[Category: Desharnais J]]
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[[Category: Desharnais, J.]]
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[[Category: Greasley SE]]
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[[Category: Greasley, S.E.]]
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[[Category: Wilson IA]]
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[[Category: Wilson, I.A.]]
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[[Category: Zhang Y]]
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[[Category: Zhang, Y.]]
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[[Category: PO4]]
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[[Category: SO4]]
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[[Category: purine biosynthesis]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:10:31 2007''
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Current revision

human glycinamide ribonucleotide Transformylase at pH 4.2

PDB ID 1meo

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