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| | ==Structure of murine cytosolic 5'-nucleotidase III complexed with uridinine monophosphate== | | ==Structure of murine cytosolic 5'-nucleotidase III complexed with uridinine monophosphate== |
| - | <StructureSection load='4fe3' size='340' side='right' caption='[[4fe3]], [[Resolution|resolution]] 1.74Å' scene=''> | + | <StructureSection load='4fe3' size='340' side='right'caption='[[4fe3]], [[Resolution|resolution]] 1.74Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fe3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FE3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FE3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fe3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FE3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FE3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2g09|2g09]], [[2g06|2g06]]</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=4fe3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fe3 OCA], [https://pdbe.org/4fe3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fe3 RCSB], [https://www.ebi.ac.uk/pdbsum/4fe3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fe3 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nt5c3, Nt5c3_predicted, rCG_52382 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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>
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| - | <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=4fe3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fe3 OCA], [http://pdbe.org/4fe3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fe3 RCSB], [http://www.ebi.ac.uk/pdbsum/4fe3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fe3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/5NT3_MOUSE 5NT3_MOUSE]] Can act both as nucleotidase and as phosphotransferase (By similarity). | + | [https://www.uniprot.org/uniprot/5NT3A_MOUSE 5NT3A_MOUSE] Nucleotidase which shows specific activity towards cytidine monophosphate (CMP) and 7-methylguanosine monophosphate (m(7)GMP). CMP seems to be the preferred substrate.[UniProtKB:Q9H0P0] |
| | <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: 5'-nucleotidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Bingman, C A]] | + | [[Category: Bingman CA]] |
| - | [[Category: Bitto, E]] | + | [[Category: Bitto E]] |
| - | [[Category: Had-like]]
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| - | [[Category: Nucleotidase]]
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| - | [[Category: Protein binding]]
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| - | [[Category: Substrate complex]]
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| Structural highlights
Function
5NT3A_MOUSE Nucleotidase which shows specific activity towards cytidine monophosphate (CMP) and 7-methylguanosine monophosphate (m(7)GMP). CMP seems to be the preferred substrate.[UniProtKB:Q9H0P0]
Publication Abstract from PubMed
Cytosolic 5'-nucleotidase III (cN-III) is responsible for selective degradation of pyrimidine 5'-monoribonucleotides during maturation of reticulocytes to erythrocytes. The lack of this enzymatic activity due to genetic aberrations or lead poisoning results in a mild to moderate nonspherocytic hemolytic anemia. In affected individuals, pyrimidine nucleotides as well as their precursor polymers and their off-path metabolites accumulate in erythrocytes, interfering with their proper function in ways that are not yet fully understood. This report describes the first X-ray structure of a catalytically inactivated variant of murine cN-III with a natural substrate, uridine 5'-monophosphate, in the active site at 1.74A resolution. The structure captures in an atomic detail the closed conformation that cN-III adopts upon substrate binding. Structure and sequence analysis coupled with enzymatic characterization of several mutants confirmed that the aromatic ring of a nitrogenous base of substrate nucleotide is stabilized by parallel pi-stacking interactions with conserved aromatic rings of Trp113 and His68. The nitrogenous base is further stabilized by T-shaped stacking with the conserved aromatic ring of Tyr114, as well as by polar contacts with side chains of Thr66 and Ser117. Two water molecules help to stabilize the nucleotide binding by bridging it to protein residues Asp72 and His68 via hydrogen bonds. Finally, fully conserved Glu96 is responsible for recognition of ribose ring via two hydrogen bonds. The presented substrate complex structure elucidates how cN-III achieves specificity for pyrimidine 5'-nucleotides and how it selects against purine 5'-nucleotides.
Structural Basis of Substrate Specificity and Selectivity of Murine Cytosolic 5'-Nucleotidase III.,Grobosky CL, Lopez JB, Rennie S, Skopelitis DJ, Wiest AT, Bingman CA, Bitto E J Mol Biol. 2012 Nov 2;423(4):540-54. doi: 10.1016/j.jmb.2012.08.014. Epub 2012, Aug 25. PMID:22925580[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Grobosky CL, Lopez JB, Rennie S, Skopelitis DJ, Wiest AT, Bingman CA, Bitto E. Structural Basis of Substrate Specificity and Selectivity of Murine Cytosolic 5'-Nucleotidase III. J Mol Biol. 2012 Nov 2;423(4):540-54. doi: 10.1016/j.jmb.2012.08.014. Epub 2012, Aug 25. PMID:22925580 doi:http://dx.doi.org/10.1016/j.jmb.2012.08.014
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