2g09: Difference between revisions
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==X-ray structure of mouse pyrimidine 5'-nucleotidase type 1, product complex== | |||
<StructureSection load='2g09' size='340' side='right'caption='[[2g09]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2g09]] is a 2 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=2G09 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2G09 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PIN:PIPERAZINE-N,N-BIS(2-ETHANESULFONIC+ACID)'>PIN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=2g09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g09 OCA], [https://pdbe.org/2g09 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2g09 RCSB], [https://www.ebi.ac.uk/pdbsum/2g09 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2g09 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g0/2g09_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=2g09 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2g09" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
== | __TOC__ | ||
< | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Bingman | [[Category: Bingman CA]] | ||
[[Category: Bitto | [[Category: Bitto E]] | ||
[[Category: Phillips Jr GN]] | |||
[[Category: Phillips | [[Category: Wesenberg GE]] | ||
[[Category: Wesenberg | |||
Latest revision as of 03:57, 21 November 2024
X-ray structure of mouse pyrimidine 5'-nucleotidase type 1, product complexX-ray structure of mouse pyrimidine 5'-nucleotidase type 1, product complex
Structural highlights
Function5NT3A_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] 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 PubMedEukaryotic 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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