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| | <StructureSection load='6kja' size='340' side='right'caption='[[6kja]], [[Resolution|resolution]] 3.06Å' scene=''> | | <StructureSection load='6kja' size='340' side='right'caption='[[6kja]], [[Resolution|resolution]] 3.06Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6kja]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KJA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KJA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6kja]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KJA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.064Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pyrB, b4245, JW4204 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI]), pyrI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aspartate_carbamoyltransferase Aspartate carbamoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.3.2 2.1.3.2] </span></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=6kja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kja OCA], [https://pdbe.org/6kja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kja RCSB], [https://www.ebi.ac.uk/pdbsum/6kja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kja ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6kja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kja OCA], [http://pdbe.org/6kja PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kja RCSB], [http://www.ebi.ac.uk/pdbsum/6kja PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kja ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PYRI_ECOLI PYRI_ECOLI]] Involved in allosteric regulation of aspartate carbamoyltransferase.[HAMAP-Rule:MF_00002] | + | [https://www.uniprot.org/uniprot/PYRB_ECOLI PYRB_ECOLI] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6kja" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6kja" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Aspartate carbamoyltransferase 3D structures|Aspartate carbamoyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aspartate carbamoyltransferase]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Ecoli]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jia, Z C]] | + | [[Category: Jia ZC]] |
| - | [[Category: Lei, Z]] | + | [[Category: Lei Z]] |
| - | [[Category: Zheng, J]] | + | [[Category: Zheng J]] |
| - | [[Category: Aspartate transcarbamoylase holoenzyme]]
| + | |
| - | [[Category: De novo pyrimidine biosynthesis]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PYRB_ECOLI
Publication Abstract from PubMed
Aspartate transcarbamoylase (ATCase) is a key enzyme which regulates and catalyzes the second step of de novo pyrimidine synthesis in all organisms. Escherichia coli ATCase is a prototypic enzyme regulated by both product feedback and substrate cooperativity, whereas human ATCase is a potential anticancer target. Through structural and biochemical analyses, we revealed that R167/130's loop region in ATCase serves as a gatekeeper for the active site, playing a new and unappreciated regulatory role in the catalytic cycle of ATCase. Based on virtual compound screening simultaneously targeting the new regulatory region and active site of human ATCase, two compounds were identified to exhibit strong inhibition of ATCase activity, proliferation of multiple cancer cell lines, and growth of xenograft tumors. Our work has not only revealed a previously unknown regulatory region of ATCase that helps uncover the catalytic and regulatory mechanism of ATCase, but also successfully guided the identification of new ATCase inhibitors for anticancer drug development using a dual-targeting strategy. DATABASE: Structure data are available in Protein Data Bank under the accession numbers: 6KJ7 (G166P ecATCase), 6KJ8 (G166P ecATCase-holo), 6KJ9 (G128/130A ecATCase), and 6KJA (G128/130A ecATCase-holo).
New regulatory mechanism-based inhibitors of aspartate transcarbamoylase for potential anticancer drug development.,Lei Z, Wang B, Lu Z, Wang N, Tan H, Zheng J, Jia Z FEBS J. 2020 Jan 22. doi: 10.1111/febs.15220. PMID:31967710[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lei Z, Wang B, Lu Z, Wang N, Tan H, Zheng J, Jia Z. New regulatory mechanism-based inhibitors of aspartate transcarbamoylase for potential anticancer drug development. FEBS J. 2020 Jan 22. doi: 10.1111/febs.15220. PMID:31967710 doi:http://dx.doi.org/10.1111/febs.15220
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