1m73
From Proteopedia
(New page: 200px<br /> <applet load="1m73" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m73, resolution 2.3Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1m73.gif|left|200px]]<br /> | + | [[Image:1m73.gif|left|200px]]<br /><applet load="1m73" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1m73" size=" | + | |
caption="1m73, resolution 2.3Å" /> | caption="1m73, resolution 2.3Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN PNP AT 2.3A RESOLUTION'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN PNP AT 2.3A RESOLUTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the | + | Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. In human, PNP is the only route for degradation of deoxyguanosine and genetic deficiency of this enzyme leads to profound T-cell mediated immunosuppression. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and its low resolution structure has been used for drug design. Here we report the structure of human PNP solved to 2.3A resolution using synchrotron radiation and cryocrystallographic techniques. This structure allowed a more precise analysis of the active site, generating a more reliable model for substrate binding. The higher resolution data allowed the identification of water molecules in the active site, which suggests binding partners for potential ligands. Furthermore, the present structure may be used in the new structure-based design of PNP inhibitors. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1M73 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] Full crystallographic information is available from [http:// | + | 1M73 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M73 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Purine-nucleoside phosphorylase]] | [[Category: Purine-nucleoside phosphorylase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Basso, L | + | [[Category: Basso, L A.]] |
[[Category: Canduri, F.]] | [[Category: Canduri, F.]] | ||
| - | [[Category: Jr., W | + | [[Category: Jr., W F.De Azevedo.]] |
| - | [[Category: Olivieri, J | + | [[Category: Olivieri, J R.]] |
| - | [[Category: Palma, M | + | [[Category: Palma, M S.]] |
| - | [[Category: Santos, D | + | [[Category: Santos, D Marangoni Dos.]] |
| - | [[Category: Santos, D | + | [[Category: Santos, D S.]] |
| - | [[Category: Santos, G | + | [[Category: Santos, G C.]] |
| - | [[Category: Silva, R | + | [[Category: Silva, R G.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: crystallography]] | [[Category: crystallography]] | ||
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[[Category: synchrotron]] | [[Category: synchrotron]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:52:12 2008'' |
Revision as of 11:52, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN PNP AT 2.3A RESOLUTION
Contents |
Overview
Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. In human, PNP is the only route for degradation of deoxyguanosine and genetic deficiency of this enzyme leads to profound T-cell mediated immunosuppression. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and its low resolution structure has been used for drug design. Here we report the structure of human PNP solved to 2.3A resolution using synchrotron radiation and cryocrystallographic techniques. This structure allowed a more precise analysis of the active site, generating a more reliable model for substrate binding. The higher resolution data allowed the identification of water molecules in the active site, which suggests binding partners for potential ligands. Furthermore, the present structure may be used in the new structure-based design of PNP inhibitors.
Disease
Known diseases associated with this structure: Neutral lipid storage disease with myopathy OMIM:[609059], Nucleoside phosphorylase deficiency, immunodeficiency due to OMIM:[164050]
About this Structure
1M73 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Purine-nucleoside phosphorylase, with EC number 2.4.2.1 Full crystallographic information is available from OCA.
Reference
Crystal structure of human purine nucleoside phosphorylase at 2.3A resolution., de Azevedo WF Jr, Canduri F, dos Santos DM, Silva RG, de Oliveira JS, de Carvalho LP, Basso LA, Mendes MA, Palma MS, Santos DS, Biochem Biophys Res Commun. 2003 Aug 29;308(3):545-52. PMID:12914785
Page seeded by OCA on Thu Feb 21 13:52:12 2008
Categories: Homo sapiens | Purine-nucleoside phosphorylase | Single protein | Basso, L A. | Canduri, F. | Jr., W F.De Azevedo. | Olivieri, J R. | Palma, M S. | Santos, D Marangoni Dos. | Santos, D S. | Santos, G C. | Silva, R G. | SO4 | Crystallography | Drug design | Purine nucleoside phosphorylase | Synchrotron
