2g08: Difference between revisions

Revision as of 04:32, 4 May 2008

X-ray structure of mouse pyrimidine 5'-nucleotidase type 1, product-transition complex analog with Aluminum fluoride

OverviewOverview

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.

About this StructureAbout this Structure

2G08 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun May 4 04:32:27 2008

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OCA

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 [[Image:2g08.gif|left|200px]]
- {{Structure
+<!--
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+The line below this paragraph, containing "STRUCTURE_2g08", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>
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-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysophospholipase Lysophospholipase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.5 3.1.1.5] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= NT5C3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
+-->
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+{{STRUCTURE_2g08|  PDB=2g08  |  SCENE=  }}
-|RELATEDENTRY=[[2bdu|2BDU]], [[2g06|2G06]], [[2g07|2G07]], [[2g09|2G09]], [[2g0a|2G0A]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2g08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g08 OCA], [http://www.ebi.ac.uk/pdbsum/2g08 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2g08 RCSB]</span>
-}}
 '''X-ray structure of mouse pyrimidine 5'-nucleotidase type 1, product-transition complex analog with Aluminum fluoride'''
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 [[Category: Jr., G N.Phillips.]]
 [[Category: Wesenberg, G E.]]
-[[Category: aah38029]]
+[[Category: Aah38029]]
-[[Category: bc038029]]
+[[Category: Bc038029]]
-[[Category: center for eukaryotic structural genomic]]
+[[Category: Center for eukaryotic structural genomic]]
-[[Category: cesg]]
+[[Category: Cesg]]
-[[Category: cytosolic 5'-nucleotidase iii]]
+[[Category: Cytosolic 5'-nucleotidase iii]]
-[[Category: lead poisoning]]
+[[Category: Lead poisoning]]
-[[Category: mm 158936]]
+[[Category: Mm 158936]]
-[[Category: nt5c3 protein]]
+[[Category: Nt5c3 protein]]
-[[Category: p5n-1]]
+[[Category: P5n-1]]
-[[Category: protein structure initiative]]
+[[Category: Protein structure initiative]]
-[[Category: psi]]
+[[Category: Psi]]
-[[Category: pyrimidine 5'-nucleotidase 1]]
+[[Category: Pyrimidine 5'-nucleotidase 1]]
-[[Category: structural genomics functional follow-up study]]
+[[Category: Structural genomics functional follow-up study]]
-[[Category: umph-1]]
+[[Category: Umph-1]]
-[[Category: uniprot q9d020]]
+[[Category: Uniprot q9d020]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 04:32:27 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:10:02 2008''