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| | ==Apo dihydroneopterin triphosphate pyrophosphohydrolase from E. coli== | | ==Apo dihydroneopterin triphosphate pyrophosphohydrolase from E. coli== |
| - | <StructureSection load='5u7e' size='340' side='right' caption='[[5u7e]], [[Resolution|resolution]] 1.94Å' scene=''> | + | <StructureSection load='5u7e' size='340' side='right'caption='[[5u7e]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5u7e]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U7E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U7E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5u7e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U7E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.942Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u7f|5u7f]], [[5u7h|5u7h]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydroneopterin_triphosphate_diphosphatase Dihydroneopterin triphosphate diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.67 3.6.1.67] </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=5u7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u7e OCA], [https://pdbe.org/5u7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u7e RCSB], [https://www.ebi.ac.uk/pdbsum/5u7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u7e ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5u7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u7e OCA], [http://pdbe.org/5u7e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u7e RCSB], [http://www.ebi.ac.uk/pdbsum/5u7e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u7e ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NUDB_ECO57 NUDB_ECO57]] Catalyzes the hydrolysis of dihydroneopterin triphosphate to dihydroneopterin monophosphate and pyrophosphate. Required for efficient folate biosynthesis. Can also hydrolyze nucleoside triphosphates with a preference for dATP.[UniProtKB:P0AFC0] | + | [https://www.uniprot.org/uniprot/NUDB_ECOLI NUDB_ECOLI] Catalyzes the hydrolysis of dihydroneopterin triphosphate to dihydroneopterin monophosphate and pyrophosphate. Required for efficient folate biosynthesis. Can also hydrolyze nucleoside triphosphates with a preference for dATP.<ref>PMID:8798731</ref> <ref>PMID:17698004</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dihydroneopterin triphosphate diphosphatase]] | + | [[Category: Escherichia coli O157:H7]] |
| - | [[Category: Hill, S E]]
| + | [[Category: Large Structures]] |
| - | [[Category: Lieberman, R L]] | + | [[Category: Hill SE]] |
| - | [[Category: Nguyen, E]] | + | [[Category: Lieberman RL]] |
| - | [[Category: Dihydroneopterin triphosphate pyrophosphohydrolase]] | + | [[Category: Nguyen E]] |
| - | [[Category: Hydrolase]] | + | |
| - | [[Category: Nudix hydrolase]]
| + | |
| Structural highlights
Function
NUDB_ECOLI Catalyzes the hydrolysis of dihydroneopterin triphosphate to dihydroneopterin monophosphate and pyrophosphate. Required for efficient folate biosynthesis. Can also hydrolyze nucleoside triphosphates with a preference for dATP.[1] [2]
Publication Abstract from PubMed
Dihydroneopterin triphosphate pyrophosphatase (DHNTPase), a member of the Mg2+ dependent Nudix hydrolase superfamily, is the recently-discovered enzyme that functions in the second step of the pterin branch of the folate biosynthetic pathway in E. coli. DHNTPase is of interest because inhibition of enzymes in bacterial folate biosynthetic pathways is a strategy for antibiotic development. We determined crystal structures of DHNTPase with and without activating, Mg2+-mimicking metals Co2+ and Ni2+. Four metal ions, identified by anomalous scattering, and stoichiometrically confirmed in solution by isothermal titration calorimetry, are held in place by Glu56 and Glu60 within the Nudix sequence motif, Glu117, waters, and a sulfate ion, of which the latter is further stabilized by a salt bridge with Lys7. In silico docking of the DHNTP substrate reveals a binding mode in which the pterin ring moiety is nestled in a largely hydrophobic pocket, the beta-phosphate activated for nucleophilic attack overlays with the crystallographic sulfate and is in line with an activated water molecule, and remaining phosphate groups are stabilized by all four identified metal ions. The structures and binding data provide new details regarding DHNTPase metal requirements, mechanism, and suggest a strategy for efficient inhibition.
Metal ion coordination in the E. coli Nudix hydrolase dihydroneopterin triphosphate pyrophosphatase: New clues into catalytic mechanism.,Hill SE, Nguyen E, Ukachukwu CU, Freeman DM, Quirk S, Lieberman RL PLoS One. 2017 Jul 25;12(7):e0180241. doi: 10.1371/journal.pone.0180241., eCollection 2017. PMID:28742822[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ O'Handley SF, Frick DN, Bullions LC, Mildvan AS, Bessman MJ. Escherichia coli orf17 codes for a nucleoside triphosphate pyrophosphohydrolase member of the MutT family of proteins. Cloning, purification, and characterization of the enzyme. J Biol Chem. 1996 Oct 4;271(40):24649-54. PMID:8798731
- ↑ Gabelli SB, Bianchet MA, Xu W, Dunn CA, Niu ZD, Amzel LM, Bessman MJ. Structure and function of the E. coli dihydroneopterin triphosphate pyrophosphatase: a Nudix enzyme involved in folate biosynthesis. Structure. 2007 Aug;15(8):1014-22. PMID:17698004 doi:S0969-2126(07)00252-3
- ↑ Hill SE, Nguyen E, Ukachukwu CU, Freeman DM, Quirk S, Lieberman RL. Metal ion coordination in the E. coli Nudix hydrolase dihydroneopterin triphosphate pyrophosphatase: New clues into catalytic mechanism. PLoS One. 2017 Jul 25;12(7):e0180241. doi: 10.1371/journal.pone.0180241., eCollection 2017. PMID:28742822 doi:http://dx.doi.org/10.1371/journal.pone.0180241
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