2g0a
From Proteopedia
(New page: 200px<br /><applet load="2g0a" size="450" color="white" frame="true" align="right" spinBox="true" caption="2g0a, resolution 2.350Å" /> '''X-ray structure of ...) |
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| - | [[Image:2g0a.gif|left|200px]]<br /><applet load="2g0a" size=" | + | [[Image:2g0a.gif|left|200px]]<br /><applet load="2g0a" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2g0a, resolution 2.350Å" /> | caption="2g0a, resolution 2.350Å" /> | ||
'''X-ray structure of mouse pyrimidine 5'-nucleotidase type 1 with lead(II) bound in active site'''<br /> | '''X-ray structure of mouse pyrimidine 5'-nucleotidase type 1 with lead(II) bound in active site'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Eukaryotic pyrimidine 5'-nucleotidase type 1 (P5N-1) catalyzes | + | 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== | ==About this Structure== | ||
| - | 2G0A 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 PB and EPE as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 2G0A 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=PB:'>PB</scene> and <scene name='pdbligand=EPE:'>EPE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=2G0A OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bingman, C | + | [[Category: Bingman, C A.]] |
[[Category: Bitto, E.]] | [[Category: Bitto, E.]] | ||
| - | [[Category: CESG, Center | + | [[Category: CESG, Center for Eukaryotic Structural Genomics.]] |
| - | [[Category: Jr., G | + | [[Category: Jr., G N.Phillips.]] |
| - | [[Category: Wesenberg, G | + | [[Category: Wesenberg, G E.]] |
[[Category: EPE]] | [[Category: EPE]] | ||
[[Category: PB]] | [[Category: PB]] | ||
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[[Category: cytosolic 5'-nucleotidase iii]] | [[Category: cytosolic 5'-nucleotidase iii]] | ||
[[Category: lead poisoning]] | [[Category: lead poisoning]] | ||
| - | [[Category: mm | + | [[Category: mm 158936]] |
[[Category: nt5c3 protein]] | [[Category: nt5c3 protein]] | ||
[[Category: p5n-1]] | [[Category: p5n-1]] | ||
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[[Category: uniprot q9d020]] | [[Category: uniprot q9d020]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:26:55 2008'' |
Revision as of 15:26, 21 February 2008
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X-ray structure of mouse pyrimidine 5'-nucleotidase type 1 with lead(II) bound in active site
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.
About this Structure
2G0A is a Single protein structure of sequence from Mus musculus with and as ligands. Active as Lysophospholipase, with EC number 3.1.1.5 Full crystallographic information is available from OCA.
Reference
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 Thu Feb 21 17:26:55 2008
Categories: Lysophospholipase | Mus musculus | Single protein | Bingman, C A. | Bitto, E. | CESG, Center for Eukaryotic Structural Genomics. | Jr., G N.Phillips. | Wesenberg, G E. | EPE | PB | Aah38029 | Bc038029 | Center for eukaryotic structural genomics | Cesg | Cytosolic 5'-nucleotidase iii | Lead poisoning | Mm 158936 | Nt5c3 protein | P5n-1 | Protein structure initiative | Psi | Pyrimidine 5'-nucleotidase 1 | Structural genomics functional follow-up study | Umph-1 | Uniprot q9d020
