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3hy3

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{{Seed}}
 
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[[Image:3hy3.jpg|left|200px]]
 
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==Structure of human MTHFS with 10-formyltetrahydrofolate==
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The line below this paragraph, containing "STRUCTURE_3hy3", creates the "Structure Box" on the page.
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<StructureSection load='3hy3' size='340' side='right'caption='[[3hy3]], [[Resolution|resolution]] 1.80&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'>[[3hy3]] 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=3HY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HY3 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]] 1.8&#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=10F:N-({4-[{[(2R,4S,4AR,6S,8AS)-2-AMINO-4-HYDROXYDECAHYDROPTERIDIN-6-YL]METHYL}(FORMYL)AMINO]PHENYL}CARBONYL)-D-GLUTAMIC+ACID'>10F</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr>
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{{STRUCTURE_3hy3| PDB=3hy3 | 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=3hy3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hy3 OCA], [https://pdbe.org/3hy3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hy3 RCSB], [https://www.ebi.ac.uk/pdbsum/3hy3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hy3 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MTHFS_HUMAN MTHFS_HUMAN] Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids.
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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/hy/3hy3_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=3hy3 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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5,10-Methenyltetrahydrofolate synthetase (MTHFS) regulates the flow of carbon through the one-carbon metabolic network, which supplies essential components for the growth and proliferation of cells. Inhibition of MTHFS in human MCF-7 breast cancer cells has been shown to arrest the growth of cells. Absence of the three-dimensional structure of human MTHFS (hMTHFS) has hampered the rational design and optimization of drug candidates. Here, we report the structures of native hMTHFS, a binary complex of hMTHFS with ADP, hMTHFS bound with the N5-iminium phosphate reaction intermediate, and an enzyme-product complex of hMTHFS. The N5-iminium phosphate captured for the first time in our crystal structure unravels a unique strategy used by hMTHFS for recognition of the substrate and provides structural basis for the regulation of enzyme activity. Binding of N10-substituted folate analogues places Y152 in the middle of the channel connecting ATP binding site with the substrate binding pocket, precluding the positioning of gamma-phosphate for a nucleophilic attack. Using the structures of hMTHFS as a guide, we have probed the role of residues surrounding the active site in catalysis by mutagenesis. The ensemble of hMTHFS structures and the mutagenesis data yield a coherent picture of the MTHFS active site, determinants of substrate specificity, and new insights into the mechanism of inhibition of hMTHFS.
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===Structure of human MTHFS with 10-formyltetrahydrofolate===
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Structural basis for the inhibition of human 5,10-methenyltetrahydrofolate synthetase by N10-substituted folate analogues.,Wu D, Li Y, Song G, Cheng C, Zhang R, Joachimiak A, Shaw N, Liu ZJ Cancer Res. 2009 Sep 15;69(18):7294-301. Epub 2009 Sep 8. PMID:19738041<ref>PMID:19738041</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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==About this Structure==
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</div>
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3HY3 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=3HY3 OCA].
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<div class="pdbe-citations 3hy3" style="background-color:#fffaf0;"></div>
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[[Category: 5-formyltetrahydrofolate cyclo-ligase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Cheng, C.]]
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[[Category: Large Structures]]
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[[Category: Li, Y.]]
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[[Category: Cheng C]]
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[[Category: Liu, Z J.]]
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[[Category: Li Y]]
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[[Category: Shaw, N.]]
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[[Category: Liu Z-J]]
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[[Category: Song, G.]]
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[[Category: Shaw N]]
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[[Category: Wu, D.]]
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[[Category: Song G]]
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[[Category: 10-formyltetrahydrofolate]]
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[[Category: Wu D]]
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[[Category: Acetylation]]
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[[Category: Antifolate]]
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[[Category: Atp-binding]]
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[[Category: Cancer]]
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[[Category: Cytoplasm]]
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[[Category: Folate-binding]]
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[[Category: Ligase]]
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[[Category: Magnesium]]
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[[Category: Nucleotide-binding]]
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[[Category: Polymorphism]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 15 13:53:59 2009''
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Current revision

Structure of human MTHFS with 10-formyltetrahydrofolate

PDB ID 3hy3

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