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| | <StructureSection load='6oiv' size='340' side='right'caption='[[6oiv]], [[Resolution|resolution]] 3.06Å' scene=''> | | <StructureSection load='6oiv' size='340' side='right'caption='[[6oiv]], [[Resolution|resolution]] 3.06Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6oiv]] 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=6OIV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OIV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6oiv]] 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=6OIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OIV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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]] 3.06Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dgt, b0160, JW0156 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=6oiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oiv OCA], [https://pdbe.org/6oiv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oiv RCSB], [https://www.ebi.ac.uk/pdbsum/6oiv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oiv ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dGTPase dGTPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.5.1 3.1.5.1] </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=6oiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oiv OCA], [http://pdbe.org/6oiv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oiv RCSB], [http://www.ebi.ac.uk/pdbsum/6oiv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oiv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DGTP_ECOLI DGTP_ECOLI]] dGTPase preferentially hydrolyzes dGTP over the other canonical NTPs.[HAMAP-Rule:MF_00030]<ref>PMID:2826481</ref> | + | [https://www.uniprot.org/uniprot/DGTP_ECOLI DGTP_ECOLI] dGTPase preferentially hydrolyzes dGTP over the other canonical NTPs.[HAMAP-Rule:MF_00030]<ref>PMID:2826481</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: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: DGTPase]]
| + | [[Category: Barnes CO]] |
| - | [[Category: Barnes, C O]] | + | [[Category: Calero G]] |
| - | [[Category: Calero, G]] | + | [[Category: Wu Y]] |
| - | [[Category: Wu, Y]] | + | |
| - | [[Category: Dntp triphosphohydrolase]]
| + | |
| - | [[Category: E. coli dgtpase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Metalloenzyme]]
| + | |
| - | [[Category: Xfel]]
| + | |
| Structural highlights
Function
DGTP_ECOLI dGTPase preferentially hydrolyzes dGTP over the other canonical NTPs.[HAMAP-Rule:MF_00030][1]
Publication Abstract from PubMed
Deoxynucleotide triphosphohydrolases (dNTPases) play a critical role in cellular survival and DNA replication through the proper maintenance of cellular dNTP pools. While the vast majority of these enzymes display broad activity toward canonical dNTPs, such as the dNTPase SAMHD1 that blocks reverse transcription of retroviruses in macrophages by maintaining dNTP pools at low levels, Escherichia coli (Ec)-dGTPase is the only known enzyme that specifically hydrolyzes dGTP. However, the mechanism behind dGTP selectivity is unclear. Here we present the free-, ligand (dGTP)- and inhibitor (GTP)-bound structures of hexameric Ec-dGTPase, including an X-ray free-electron laser structure of the free Ec-dGTPase enzyme to 3.2 A. To obtain this structure, we developed a method that applied UV-fluorescence microscopy, video analysis, and highly automated goniometer-based instrumentation to map and rapidly position individual crystals randomly located on fixed target holders, resulting in the highest indexing rates observed for a serial femtosecond crystallography experiment. Our structures show a highly dynamic active site where conformational changes are coupled to substrate (dGTP), but not inhibitor binding, since GTP locks dGTPase in its apo- form. Moreover, despite no sequence homology, Ec-dGTPase and SAMHD1 share similar active-site and HD motif architectures; however, Ec-dGTPase residues at the end of the substrate-binding pocket mimic Watson-Crick interactions providing guanine base specificity, while a 7-A cleft separates SAMHD1 residues from dNTP bases, abolishing nucleotide-type discrimination. Furthermore, the structures shed light on the mechanism by which long distance binding (25 A) of single-stranded DNA in an allosteric site primes the active site by conformationally "opening" a tyrosine gate allowing enhanced substrate binding.
The crystal structure of dGTPase reveals the molecular basis of dGTP selectivity.,Barnes CO, Wu Y, Song J, Lin G, Baxter EL, Brewster AS, Nagarajan V, Holmes A, Soltis SM, Sauter NK, Ahn J, Cohen AE, Calero G Proc Natl Acad Sci U S A. 2019 May 7;116(19):9333-9339. doi:, 10.1073/pnas.1814999116. Epub 2019 Apr 24. PMID:31019074[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Seto D, Bhatnagar SK, Bessman MJ. The purification and properties of deoxyguanosine triphosphate triphosphohydrolase from Escherichia coli. J Biol Chem. 1988 Jan 25;263(3):1494-9. PMID:2826481
- ↑ Barnes CO, Wu Y, Song J, Lin G, Baxter EL, Brewster AS, Nagarajan V, Holmes A, Soltis SM, Sauter NK, Ahn J, Cohen AE, Calero G. The crystal structure of dGTPase reveals the molecular basis of dGTP selectivity. Proc Natl Acad Sci U S A. 2019 May 7;116(19):9333-9339. doi:, 10.1073/pnas.1814999116. Epub 2019 Apr 24. PMID:31019074 doi:http://dx.doi.org/10.1073/pnas.1814999116
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