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| - | [[Image:1s1m.jpg|left|200px]] | |
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| - | {{Structure
| + | ==Crystal Structure of E. Coli CTP Synthetase== |
| - | |PDB= 1s1m |SIZE=350|CAPTION= <scene name='initialview01'>1s1m</scene>, resolution 2.30Å
| + | <StructureSection load='1s1m' size='340' side='right'caption='[[1s1m]], [[Resolution|resolution]] 2.30Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene> and <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>
| + | <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> |
| - | |ACTIVITY= [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]
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | |GENE= PYRG, B2780, C3345, Z4095, ECS3640, SF2795, S2989 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
| + | <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> |
| - | }}
| + | <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> |
| - | | + | </table> |
| - | '''Crystal Structure of E. Coli CTP Synthetase'''
| + | == Function == |
| - | | + | [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] |
| - | | + | == Evolutionary Conservation == |
| - | ==Overview== | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | 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.
| + | Check<jmol> |
| - | | + | <jmolCheckbox> |
| - | ==About this Structure== | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/s1/1s1m_consurf.spt"</scriptWhenChecked> |
| - | 1S1M is a [[Single protein]] structure of sequence 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=1S1M OCA].
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | | + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | ==Reference==
| + | </jmolCheckbox> |
| - | 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://www.ncbi.nlm.nih.gov/pubmed/15157079 15157079]
| + | </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]. |
| - | [[Category: CTP synthase]]
| + | <div style="clear:both"></div> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Escherichia coli]] | | [[Category: Escherichia coli]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Anderson, P M.]] | + | [[Category: Anderson PM]] |
| - | [[Category: Baldwin, E P.]] | + | [[Category: Baldwin EP]] |
| - | [[Category: Endrizzi, J A.]] | + | [[Category: Endrizzi JA]] |
| - | [[Category: Kim, H.]] | + | [[Category: Kim H]] |
| - | [[Category: IOD]]
| + | |
| - | [[Category: MG]]
| + | |
| - | [[Category: MPD]]
| + | |
| - | [[Category: SO4]]
| + | |
| - | [[Category: ammonia lyase]]
| + | |
| - | [[Category: ammonia tunnel]]
| + | |
| - | [[Category: class-ii glutamine amidotransferase]]
| + | |
| - | [[Category: ctp synthetase]]
| + | |
| - | [[Category: cytidine 5'-triphosphate synthase]]
| + | |
| - | [[Category: utp:ammonia ligase (adp-forming)]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:59:12 2008''
| + | |
