2a9w

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{{Seed}}
 
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[[Image:2a9w.png|left|200px]]
 
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==E. coli TS complexed with dUMP and inhibitor GA9==
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The line below this paragraph, containing "STRUCTURE_2a9w", creates the "Structure Box" on the page.
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<StructureSection load='2a9w' size='340' side='right'caption='[[2a9w]], [[Resolution|resolution]] 1.65&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'>[[2a9w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A9W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A9W 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]] 1.65&#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=2BR:2-BROMOPHENOL'>2BR</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CXM:N-CARBOXYMETHIONINE'>CXM</scene>, <scene name='pdbligand=GA9:3,3-BIS(3-BROMO-4-HYDROXYPHENYL)-7-CHLORO-1H,3H-BENZO[DE]ISOCHROMEN-1-ONE'>GA9</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
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{{STRUCTURE_2a9w| PDB=2a9w | 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=2a9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a9w OCA], [https://pdbe.org/2a9w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a9w RCSB], [https://www.ebi.ac.uk/pdbsum/2a9w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a9w ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TYSY_ECOLI TYSY_ECOLI] Provides the sole de novo source of dTMP for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation.
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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/a9/2a9w_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=2a9w 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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The ternary complex crystal structures of Cryptococcus neoformans and Escherichia coli thymidylate synthase (TS) suggest mechanisms of species-specific inhibition of a highly conserved protein. The 2.1 Angstrom structure of C. neoformans TS cocrystallized with substrate and the cofactor analog CB3717 shows that the binding sites for substrate and cofactor are highly conserved with respect to human TS, but that the structure of the cofactor-binding site of C. neoformans TS is less constrained by surrounding residues. This feature might allow C. neoformans TS to form TS-dUMP-inhibitor complexes with a greater range of antifolates than human TS. 3',3''-Dibromophenol-4-chloro-1,8-naphthalein (GA9) selectively inhibits both E. coli TS and C. neoformans TS (K(i) = 4 microM) over human TS (K(i) &gt;&gt; 245 microM). The E. coli TS-dUMP-GA9 complex is in an open conformation, similar to that of the apoenzyme crystal structure. The GA9-binding site overlaps the binding site of the pABA-glutamyl moiety of the cofactor. The fact that human apoTS can adopt an unusual fold in which the GA9-binding site is disordered may explain the poor affinity of GA9 for the human enzyme. These observations highlight the critical need to incorporate multiple target conformations in any computational attempt to facilitate drug discovery.
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===E. coli TS complexed with dUMP and inhibitor GA9===
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The structure of Cryptococcus neoformans thymidylate synthase suggests strategies for using target dynamics for species-specific inhibition.,Finer-Moore JS, Anderson AC, O'Neil RH, Costi MP, Ferrari S, Krucinski J, Stroud RM Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1320-34. Epub 2005, Sep 28. PMID:16204883<ref>PMID:16204883</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 2a9w" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_16204883}}, adds the Publication Abstract to the page
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*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 16204883 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16204883}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2A9W is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A9W OCA].
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==Reference==
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<ref group="xtra">PMID:16204883</ref><references group="xtra"/>
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[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Thymidylate synthase]]
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[[Category: Large Structures]]
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[[Category: Anderson, A C.]]
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[[Category: Anderson AC]]
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[[Category: Costi, M P.]]
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[[Category: Costi MP]]
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[[Category: Ferrari, S.]]
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[[Category: Ferrari S]]
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[[Category: Finer-Moore, J S.]]
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[[Category: Finer-Moore JS]]
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[[Category: Krucinski, J.]]
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[[Category: Krucinski J]]
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[[Category: Neil, R H.O.]]
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[[Category: O'Neil RH]]
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[[Category: Stroud, R M.]]
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[[Category: Stroud RM]]
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[[Category: Protein-inhibitor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 06:49:16 2009''
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Current revision

E. coli TS complexed with dUMP and inhibitor GA9

PDB ID 2a9w

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