2g07: Difference between revisions

Revision as of 18:26, 21 February 2008

X-ray structure of mouse pyrimidine 5'-nucleotidase type 1, phospho-enzyme intermediate analog with Beryllium 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

2G07 is a Single protein structure of sequence from Mus musculus with as ligand. Active as Lysophospholipase, with EC number 3.1.1.5 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

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-[[Image:2g07.gif|left|200px]]<br /><applet load="2g07" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2g07.gif|left|200px]]<br /><applet load="2g07" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2g07, resolution 2.300&Aring;" />
 '''X-ray structure of mouse pyrimidine 5'-nucleotidase type 1, phospho-enzyme intermediate analog with Beryllium fluoride'''<br />
 ==Overview==
-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.
 ==About this Structure==
-G07 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2G07 OCA].
+G07 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G07 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Mus musculus]]
 [[Category: Single protein]]
-[[Category: Bingman, C.A.]]
+[[Category: Bingman, C A.]]
 [[Category: Bitto, E.]]
-[[Category: CESG, Center.for.Eukaryotic.Structural.Genomics.]]
+[[Category: CESG, Center for Eukaryotic Structural Genomics.]]
-[[Category: Jr., G.N.Phillips.]]
+[[Category: Jr., G N.Phillips.]]
-[[Category: Wesenberg, G.E.]]
+[[Category: Wesenberg, G E.]]
 [[Category: MG]]
 [[Category: aah38029]]
@@ Line 26: / Line 26: @@
 [[Category: cytosolic 5'-nucleotidase iii]]
 [[Category: lead poisoning]]
-[[Category: mm.158936]]
+[[Category: mm 158936]]
 [[Category: nt5c3 protein]]
 [[Category: p5n-1]]
@@ Line 36: / Line 36: @@
 [[Category: uniprot q9d020]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:52:24 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:26:52 2008''