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2g06

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[[Image:2g06.gif|left|200px]]
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==X-ray structure of mouse pyrimidine 5'-nucleotidase type 1, with bound magnesium(II)==
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<StructureSection load='2g06' size='340' side='right' caption='[[2g06]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
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{{Structure
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== Structural highlights ==
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|PDB= 2g06 |SIZE=350|CAPTION= <scene name='initialview01'>2g06</scene>, resolution 2.250&Aring;
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<table><tr><td colspan='2'>[[2g06]] is a 2 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=2G06 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2G06 FirstGlance]. <br>
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|SITE=
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PIN:PIPERAZINE-N,N-BIS(2-ETHANESULFONIC+ACID)'>PIN</scene></td></tr>
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|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PIN:PIPERAZINE-N,N&#39;-BIS(2-ETHANESULFONIC+ACID)'>PIN</scene>
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<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>
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|ACTIVITY= <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>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2bdu|2bdu]], [[2g07|2g07]], [[2g08|2g08]], [[2g09|2g09]], [[2g0a|2g0a]]</td></tr>
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|GENE= Nt5c3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nt5c3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
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|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=COG4359 COG4359], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam05822 UMPH-1]</span>
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<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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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2g06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g06 OCA], [http://www.ebi.ac.uk/pdbsum/2g06 PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=2g06 RCSB]</span>
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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=2g06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g06 OCA], [http://pdbe.org/2g06 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2g06 RCSB], [http://www.ebi.ac.uk/pdbsum/2g06 PDBsum], [http://www.topsan.org/Proteins/CESG/2g06 TOPSAN]</span></td></tr>
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}}
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</table>
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== Function ==
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'''X-ray structure of mouse pyrimidine 5'-nucleotidase type 1, with bound magnesium(II)'''
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[[http://www.uniprot.org/uniprot/5NT3_MOUSE 5NT3_MOUSE]] Can act both as nucleotidase and as phosphotransferase (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==Overview==
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g0/2g06_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2g06 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
Eukaryotic pyrimidine 5'-nucleotidase type 1 (P5N-1) catalyzes dephosphorylation of pyrimidine 5'-mononucleotides. Deficiency of P5N-1 activity in red blood cells results in nonspherocytic hemolytic anemia. The enzyme deficiency is either familial or can be acquired through lead poisoning. We present the crystal structure of mouse P5N-1 refined to 2.35 A resolution. The mouse P5N-1 has a 92% sequence identity to its human counterpart. The structure revealed that P5N-1 adopts a fold similar to enzymes of the haloacid dehydrogenase superfamily. The active site of this enzyme is structurally highly similar to those of phosphoserine phosphatases. We propose a catalytic mechanism for P5N-1 that is also similar to that of phosphoserine phosphatases and provide experimental evidence for the mechanism in the form of structures of several reaction cycle states, including: 1) P5N-1 with bound Mg(II) at 2.25 A, 2) phosphoenzyme intermediate analog at 2.30 A, 3) product-transition complex analog at 2.35 A, and 4) product complex at 2.1A resolution with phosphate bound in the active site. Furthermore the structure of Pb(II)-inhibited P5N-1 (at 2.35 A) revealed that Pb(II) binds within the active site in a way that compromises function of the cationic cavity, which is required for the recognition and binding of the phosphate group of nucleotides.
Eukaryotic pyrimidine 5'-nucleotidase type 1 (P5N-1) catalyzes dephosphorylation of pyrimidine 5'-mononucleotides. Deficiency of P5N-1 activity in red blood cells results in nonspherocytic hemolytic anemia. The enzyme deficiency is either familial or can be acquired through lead poisoning. We present the crystal structure of mouse P5N-1 refined to 2.35 A resolution. The mouse P5N-1 has a 92% sequence identity to its human counterpart. The structure revealed that P5N-1 adopts a fold similar to enzymes of the haloacid dehydrogenase superfamily. The active site of this enzyme is structurally highly similar to those of phosphoserine phosphatases. We propose a catalytic mechanism for P5N-1 that is also similar to that of phosphoserine phosphatases and provide experimental evidence for the mechanism in the form of structures of several reaction cycle states, including: 1) P5N-1 with bound Mg(II) at 2.25 A, 2) phosphoenzyme intermediate analog at 2.30 A, 3) product-transition complex analog at 2.35 A, and 4) product complex at 2.1A resolution with phosphate bound in the active site. Furthermore the structure of Pb(II)-inhibited P5N-1 (at 2.35 A) revealed that Pb(II) binds within the active site in a way that compromises function of the cationic cavity, which is required for the recognition and binding of the phosphate group of nucleotides.
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==About this Structure==
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Structure of pyrimidine 5'-nucleotidase type 1. Insight into mechanism of action and inhibition during lead poisoning.,Bitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN Jr J Biol Chem. 2006 Jul 21;281(29):20521-9. Epub 2006 May 3. PMID:16672222<ref>PMID:16672222</ref>
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2G06 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G06 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structure of pyrimidine 5'-nucleotidase type 1. Insight into mechanism of action and inhibition during lead poisoning., Bitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN Jr, J Biol Chem. 2006 Jul 21;281(29):20521-9. Epub 2006 May 3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16672222 16672222]
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</div>
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<div class="pdbe-citations 2g06" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: 5'-nucleotidase]]
[[Category: 5'-nucleotidase]]
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[[Category: Mus musculus]]
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[[Category: Lk3 transgenic mice]]
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[[Category: Single protein]]
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[[Category: Bingman, C A]]
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[[Category: Bingman, C A.]]
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[[Category: Bitto, E]]
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[[Category: Bitto, E.]]
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[[Category: Structural genomic]]
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[[Category: CESG, Center for Eukaryotic Structural Genomics.]]
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[[Category: Phillips, G N]]
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[[Category: Jr., G N.Phillips.]]
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[[Category: Wesenberg, G E]]
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[[Category: Wesenberg, G E.]]
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[[Category: Aah38029]]
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[[Category: aah38029]]
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[[Category: Bc038029]]
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[[Category: bc038029]]
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[[Category: Cesg]]
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[[Category: center for eukaryotic structural genomic]]
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[[Category: Cytosolic 5'-nucleotidase iii]]
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[[Category: cesg]]
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[[Category: Hydrolase]]
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[[Category: cytosolic 5'-nucleotidase iii]]
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[[Category: Lead poisoning]]
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[[Category: lead poisoning]]
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[[Category: Mm 158936]]
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[[Category: mm 158936]]
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[[Category: Nt5c3 protein]]
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[[Category: nt5c3 protein]]
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[[Category: P5n-1]]
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[[Category: p5n-1]]
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[[Category: PSI, Protein structure initiative]]
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[[Category: protein structure initiative]]
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[[Category: Pyrimidine 5'-nucleotidase 1]]
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[[Category: psi]]
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[[Category: Umph-1]]
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[[Category: pyrimidine 5'-nucleotidase 1]]
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[[Category: Uniprot q9d020]]
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[[Category: structural genomics functional follow-up study]]
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[[Category: umph-1]]
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[[Category: uniprot q9d020]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 06:25:44 2008''
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Current revision

X-ray structure of mouse pyrimidine 5'-nucleotidase type 1, with bound magnesium(II)

2g06, resolution 2.25Å

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