1s1m

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(New page: 200px<br /><applet load="1s1m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s1m, resolution 2.30&Aring;" /> '''Crystal Structure of...)
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[[Image:1s1m.jpg|left|200px]]<br /><applet load="1s1m" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1s1m, resolution 2.30&Aring;" />
 
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'''Crystal Structure of E. Coli CTP Synthetase'''<br />
 
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==Overview==
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==Crystal Structure of E. Coli CTP Synthetase==
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Cytidine triphosphate synthetases (CTPSs) produce CTP from UTP and, glutamine, and regulate intracellular CTP levels through interactions with, the four ribonucleotide triphosphates. We solved the 2.3-A resolution, crystal structure of Escherichia coli CTPS using Hg-MAD phasing. The, structure reveals a nearly symmetric 222 tetramer, in which each, bifunctional monomer contains a dethiobiotin synthetase-like amidoligase, N-terminal domain and a Type 1 glutamine amidotransferase C-terminal, domain. For each amidoligase active site, essential ATP- and UTP-binding, surfaces are contributed by three monomers, suggesting that activity, requires tetramer formation, and that a nucleotide-dependent, dimer-tetramer equilibrium contributes to the observed positive, cooperativity. A gated channel that spans 25 A between the glutamine, hydrolysis and amidoligase active sites provides a path for ammonia, diffusion. The channel is accessible to solvent at the base of a cleft, adjoining the glutamine hydrolysis active site, providing an entry point, for exogenous ammonia. Guanine nucleotide binding sites of structurally, related GTPases superimpose on this cleft, providing insights into, allosteric regulation by GTP. Mutations that confer nucleoside drug, resistance and release CTP inhibition map to a pocket that neighbors the, UTP-binding site and can accommodate a pyrimidine ring. Its location, suggests that competitive feedback inhibition is affected via a distinct, product/drug binding site that overlaps the substrate triphosphate binding, site. Overall, the E. coli structure provides a framework for homology, modeling of other CTPSs and structure-based design of anti-CTPS, therapeutics.
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<StructureSection load='1s1m' size='340' side='right'caption='[[1s1m]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1s1m]] is a 2 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=1S1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S1M FirstGlance]. <br>
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1S1M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SO4, MG, IOD and MPD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/CTP_synthase CTP synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.2 6.3.4.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S1M 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]] 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=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=1s1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s1m OCA], [https://pdbe.org/1s1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s1m RCSB], [https://www.ebi.ac.uk/pdbsum/1s1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s1m ProSAT]</span></td></tr>
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Crystal structure of Escherichia coli cytidine triphosphate synthetase, a nucleotide-regulated glutamine amidotransferase/ATP-dependent amidoligase fusion protein and homologue of anticancer and antiparasitic drug targets., Endrizzi JA, Kim H, Anderson PM, Baldwin EP, Biochemistry. 2004 Jun 1;43(21):6447-63. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15157079 15157079]
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</table>
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[[Category: CTP synthase]]
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== Function ==
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[https://www.uniprot.org/uniprot/PYRG_ECOLI PYRG_ECOLI] Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen.[HAMAP-Rule:MF_01227]
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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/s1/1s1m_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=1s1m ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Anderson, P.M.]]
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[[Category: Anderson PM]]
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[[Category: Baldwin, E.P.]]
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[[Category: Baldwin EP]]
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[[Category: Endrizzi, J.A.]]
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[[Category: Endrizzi JA]]
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[[Category: Kim, H.]]
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[[Category: Kim H]]
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[[Category: IOD]]
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[[Category: MG]]
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[[Category: MPD]]
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[[Category: SO4]]
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[[Category: ammonia lyase]]
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[[Category: ammonia tunnel]]
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[[Category: class-ii glutamine amidotransferase]]
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[[Category: ctp synthetase]]
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[[Category: cytidine 5'-triphosphate synthase]]
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[[Category: utp:ammonia ligase (adp-forming)]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 02:02:24 2007''
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Current revision

Crystal Structure of E. Coli CTP Synthetase

PDB ID 1s1m

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