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| | ==Crystal structure of the 5'-deoxynucleotidase YfbR== | | ==Crystal structure of the 5'-deoxynucleotidase YfbR== |
| - | <StructureSection load='2paq' size='340' side='right' caption='[[2paq]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='2paq' size='340' side='right'caption='[[2paq]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2paq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1wph 1wph]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PAQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PAQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2paq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecoli Ecoli]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1wph 1wph]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PAQ FirstGlance]. <br> |
| | </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> | | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2par|2par]], [[2pau|2pau]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2par|2par]], [[2pau|2pau]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">yfbR, b2291, JW2288 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">yfbR, b2291, JW2288 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/5'-nucleotidase 5'-nucleotidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.5 3.1.3.5] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/5'-nucleotidase 5'-nucleotidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.5 3.1.3.5] </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=2paq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2paq OCA], [http://pdbe.org/2paq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2paq RCSB], [http://www.ebi.ac.uk/pdbsum/2paq PDBsum], [http://www.topsan.org/Proteins/MCSG/2paq TOPSAN]</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=2paq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2paq OCA], [https://pdbe.org/2paq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2paq RCSB], [https://www.ebi.ac.uk/pdbsum/2paq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2paq ProSAT], [https://www.topsan.org/Proteins/MCSG/2paq TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/5DNU_ECOLI 5DNU_ECOLI]] Essential component of the deoxycytidine triphosphate (dCTP) pathway for de novo synthesis of thymidylate. Catalyzes the strictly specific dephosphorylation of 2'-deoxyribonucleoside 5'-monophosphates (dAMP, dGMP, dTMP, dUMP, dIMP and dCMP) and does not dephosphorylate 5'-ribonucleotides or ribonucleoside 3'-monophosphates.<ref>PMID:15489502</ref> <ref>PMID:17827303</ref> <ref>PMID:18353368</ref> | + | [[https://www.uniprot.org/uniprot/5DNU_ECOLI 5DNU_ECOLI]] Essential component of the deoxycytidine triphosphate (dCTP) pathway for de novo synthesis of thymidylate. Catalyzes the strictly specific dephosphorylation of 2'-deoxyribonucleoside 5'-monophosphates (dAMP, dGMP, dTMP, dUMP, dIMP and dCMP) and does not dephosphorylate 5'-ribonucleotides or ribonucleoside 3'-monophosphates.<ref>PMID:15489502</ref> <ref>PMID:17827303</ref> <ref>PMID:18353368</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pa/2paq_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pa/2paq_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | [[Category: 5'-nucleotidase]] | | [[Category: 5'-nucleotidase]] |
| | [[Category: Ecoli]] | | [[Category: Ecoli]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Chruszcz, M]] | | [[Category: Chruszcz, M]] |
| | [[Category: Cymborowski, M]] | | [[Category: Cymborowski, M]] |
| Structural highlights
Function
[5DNU_ECOLI] Essential component of the deoxycytidine triphosphate (dCTP) pathway for de novo synthesis of thymidylate. Catalyzes the strictly specific dephosphorylation of 2'-deoxyribonucleoside 5'-monophosphates (dAMP, dGMP, dTMP, dUMP, dIMP and dCMP) and does not dephosphorylate 5'-ribonucleotides or ribonucleoside 3'-monophosphates.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
HD-domain phosphohydrolases have nucleotidase and phosphodiesterase activities and play important roles in the metabolism of nucleotides and in signaling. We present three 2.1-A-resolution crystal structures (one in the free state and two complexed with natural substrates) of an HD-domain phosphohydrolase, the Escherichia coli 5'-nucleotidase YfbR. The free-state structure of YfbR contains a large cavity accommodating the metal-coordinating HD motif (H33, H68, D69, and D137) and other conserved residues (R18, E72, and D77). Alanine scanning mutagenesis confirms that these residues are important for activity. Two structures of the catalytically inactive mutant E72A complexed with Co(2+) and either thymidine-5'-monophosphate or 2'-deoxyriboadenosine-5'-monophosphate disclose the novel binding mode of deoxyribonucleotides in the active site. Residue R18 stabilizes the phosphate on the Co(2+), and residue D77 forms a strong hydrogen bond critical for binding the ribose. The indole side chain of W19 is located close to the 2'-carbon atom of the deoxyribose moiety and is proposed to act as the selectivity switch for deoxyribonucleotide, which is supported by comparison to YfdR, another 5'-nucleotidase in E. coli. The nucleotide bases of both deoxyriboadenosine-5'-monophosphate and thymidine-5'-monophosphate make no specific hydrogen bonds with the protein, explaining the lack of nucleotide base selectivity. The YfbR E72A substrate complex structures also suggest a plausible single-step nucleophilic substitution mechanism. This is the first proposed molecular mechanism for an HD-domain phosphohydrolase based directly on substrate-bound crystal structures.
Structural insight into the mechanism of substrate specificity and catalytic activity of an HD-domain phosphohydrolase: the 5'-deoxyribonucleotidase YfbR from Escherichia coli.,Zimmerman MD, Proudfoot M, Yakunin A, Minor W J Mol Biol. 2008 Apr 18;378(1):215-26. Epub 2008 Mar 4. PMID:18353368[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Proudfoot M, Kuznetsova E, Brown G, Rao NN, Kitagawa M, Mori H, Savchenko A, Yakunin AF. General enzymatic screens identify three new nucleotidases in Escherichia coli. Biochemical characterization of SurE, YfbR, and YjjG. J Biol Chem. 2004 Dec 24;279(52):54687-94. Epub 2004 Oct 15. PMID:15489502 doi:http://dx.doi.org/M411023200
- ↑ Weiss B. The deoxycytidine pathway for thymidylate synthesis in Escherichia coli. J Bacteriol. 2007 Nov;189(21):7922-6. Epub 2007 Sep 7. PMID:17827303 doi:http://dx.doi.org/10.1128/JB.00461-07
- ↑ Zimmerman MD, Proudfoot M, Yakunin A, Minor W. Structural insight into the mechanism of substrate specificity and catalytic activity of an HD-domain phosphohydrolase: the 5'-deoxyribonucleotidase YfbR from Escherichia coli. J Mol Biol. 2008 Apr 18;378(1):215-26. Epub 2008 Mar 4. PMID:18353368 doi:S0022-2836(08)00233-7
- ↑ Zimmerman MD, Proudfoot M, Yakunin A, Minor W. Structural insight into the mechanism of substrate specificity and catalytic activity of an HD-domain phosphohydrolase: the 5'-deoxyribonucleotidase YfbR from Escherichia coli. J Mol Biol. 2008 Apr 18;378(1):215-26. Epub 2008 Mar 4. PMID:18353368 doi:S0022-2836(08)00233-7
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