8i9o
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 8i9o is ON HOLD Authors: Guo, C.J., Liu, J.L. Description: ecCTPS with CTP, NADH and DON Category: Unreleased Structures Category: Guo, C.J...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==ecCTPS filament bound with CTP, NADH, DON== | |
| + | <StructureSection load='8i9o' size='340' side='right'caption='[[8i9o]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8i9o]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_'BL21-Gold(DE3)pLysS_AG' Escherichia coli 'BL21-Gold(DE3)pLysS AG']. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8I9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8I9O FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.9Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADE:ADENINE'>ADE</scene>, <scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ONL:5-OXO-L-NORLEUCINE'>ONL</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=8i9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8i9o OCA], [https://pdbe.org/8i9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8i9o RCSB], [https://www.ebi.ac.uk/pdbsum/8i9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8i9o ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cytidine triphosphate synthase (CTPS) plays a pivotal role in the de novo synthesis of cytidine triphosphate (CTP), a fundamental building block for RNA and DNA that is essential for life. CTPS is capable of directly binding to all four nucleotide triphosphates: adenine triphosphate, uridine triphosphate, CTP, and guanidine triphosphate. Furthermore, CTPS can form cytoophidia in vivo and metabolic filaments in vitro, undergoing regulation at multiple levels. CTPS is considered a potential therapeutic target for combating invasions or infections by viral or prokaryotic pathogens. Utilizing cryo-electron microscopy, we determined the structure of Escherichia coli CTPS (ecCTPS) filament in complex with CTP, nicotinamide adenine dinucleotide (NADH), and the covalent inhibitor 6-diazo-5-oxo- l-norleucine (DON), achieving a resolution of 2.9 A. We constructed a phylogenetic tree based on differences in filament-forming interfaces and designed a variant to validate our hypothesis, providing an evolutionary perspective on CTPS filament formation. Our computational analysis revealed a solvent-accessible ammonia tunnel upon DON binding. Through comparative structural analysis, we discern a distinct mode of CTP binding of ecCTPS that differs from eukaryotic counterparts. Combining biochemical assays and structural analysis, we determined and validated the synergistic inhibitory effects of CTP with NADH or adenine on CTPS. Our results expand our comprehension of the diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS. | ||
| - | + | Filamentation and inhibition of prokaryotic CTP synthase with ligands.,Guo C, Wang Z, Liu JL mLife. 2024 May 2;3(2):240-250. doi: 10.1002/mlf2.12119. eCollection 2024 Jun. PMID:38948148<ref>PMID:38948148</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Guo | + | <div class="pdbe-citations 8i9o" style="background-color:#fffaf0;"></div> |
| - | [[Category: Liu | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Guo CJ]] | ||
| + | [[Category: Liu JL]] | ||
Current revision
ecCTPS filament bound with CTP, NADH, DON
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