2bdu
From Proteopedia
(New page: 200px<br /><applet load="2bdu" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bdu, resolution 2.350Å" /> '''X-Ray Structure of ...) |
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| - | [[Image:2bdu.jpg|left|200px]]<br /><applet load="2bdu" size=" | + | [[Image:2bdu.jpg|left|200px]]<br /><applet load="2bdu" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2bdu, resolution 2.350Å" /> | caption="2bdu, resolution 2.350Å" /> | ||
'''X-Ray Structure of a Cytosolic 5'-Nucleotidase III from Mus Musculus MM.158936'''<br /> | '''X-Ray Structure of a Cytosolic 5'-Nucleotidase III from Mus Musculus MM.158936'''<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== | ||
| - | 2BDU 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 EPE as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 2BDU 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=EPE:'>EPE</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BDU OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bae, E.]] | [[Category: Bae, E.]] | ||
| - | [[Category: Bingman, C | + | [[Category: Bingman, C A.]] |
[[Category: Bitto, E.]] | [[Category: Bitto, E.]] | ||
| - | [[Category: CESG, Center | + | [[Category: CESG, Center for Eukaryotic Structural Genomics.]] |
| - | [[Category: Han, B | + | [[Category: Han, B W.]] |
| - | [[Category: Jr., G | + | [[Category: Jr., G N.Phillips.]] |
| - | [[Category: Wesenberg, G | + | [[Category: Wesenberg, G E.]] |
[[Category: EPE]] | [[Category: EPE]] | ||
[[Category: aah38029]] | [[Category: aah38029]] | ||
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[[Category: cesg]] | [[Category: cesg]] | ||
[[Category: cytosolic 5'-nucleotidase iii]] | [[Category: cytosolic 5'-nucleotidase iii]] | ||
| - | [[Category: mm | + | [[Category: mm 158936]] |
[[Category: nt5c3 protein]] | [[Category: nt5c3 protein]] | ||
[[Category: protein structure initiative]] | [[Category: protein structure initiative]] | ||
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[[Category: umph-1]] | [[Category: umph-1]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:36:49 2008'' |
Revision as of 14:37, 21 February 2008
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X-Ray Structure of a Cytosolic 5'-Nucleotidase III from Mus Musculus MM.158936
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
2BDU is a Single protein structure of sequence from Mus musculus with as ligand. Active as 5'-nucleotidase, with EC number 3.1.3.5 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 16:36:49 2008
Categories: 5'-nucleotidase | Mus musculus | Single protein | Bae, E. | Bingman, C A. | Bitto, E. | CESG, Center for Eukaryotic Structural Genomics. | Han, B W. | Jr., G N.Phillips. | Wesenberg, G E. | EPE | Aah38029 | Bc038029 | Center for eukaryotic structural genomics | Cesg | Cytosolic 5'-nucleotidase iii | Mm 158936 | Nt5c3 protein | Protein structure initiative | Psi | Structural genomics | Umph-1
