1pf7
From Proteopedia
(New page: 200px<br /> <applet load="1pf7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pf7, resolution 2.60Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1pf7.gif|left|200px]]<br /> | + | [[Image:1pf7.gif|left|200px]]<br /><applet load="1pf7" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1pf7, resolution 2.60Å" /> | caption="1pf7, resolution 2.60Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH IMMUCILLIN H'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH IMMUCILLIN H'''<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. PNP is a target for inhibitor development aiming at T-cell immune response modulation. This work reports on the crystallographic study of the complex of human PNP-immucillin-H (HsPNP-ImmH) solved at 2.6A resolution using synchrotron radiation. Immucillin-H (ImmH) inhibits the growth of malignant T-cell lines in the presence of deoxyguanosine without affecting non-T-cell tumor lines. ImmH inhibits activated normal human T cells after antigenic stimulation in vitro. These biological effects of ImmH suggest that this agent may have utility in the treatment of certain human diseases characterized by abnormal T-cell growth or activation. This is the first structural report of human PNP complexed with immucillin-H. The comparison of the complex HsPNP-ImmH with recent crystallographic structures of human PNP explains the high specificity of immucillin-H for human PNP. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1PF7 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 and IMH as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1PF7 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> and <scene name='pdbligand=IMH:'>IMH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1PF7 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: Dias, M | + | [[Category: Dias, M V.B.]] |
| - | [[Category: Jr., W | + | [[Category: Jr., W F.De Azevedo.]] |
| - | [[Category: Mendes, M | + | [[Category: Mendes, M A.]] |
| - | [[Category: Palma, M | + | [[Category: Palma, M S.]] |
| - | [[Category: Pereira, J | + | [[Category: Pereira, J H.]] |
| - | [[Category: Santos, D | + | [[Category: Santos, D M.Dos.]] |
| - | [[Category: Santos, D | + | [[Category: Santos, D S.]] |
| - | [[Category: Silva, R | + | [[Category: Silva, R G.]] |
[[Category: IMH]] | [[Category: IMH]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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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 14:28:09 2008'' |
Revision as of 12:28, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH IMMUCILLIN H
Contents |
Overview
Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation. This work reports on the crystallographic study of the complex of human PNP-immucillin-H (HsPNP-ImmH) solved at 2.6A resolution using synchrotron radiation. Immucillin-H (ImmH) inhibits the growth of malignant T-cell lines in the presence of deoxyguanosine without affecting non-T-cell tumor lines. ImmH inhibits activated normal human T cells after antigenic stimulation in vitro. These biological effects of ImmH suggest that this agent may have utility in the treatment of certain human diseases characterized by abnormal T-cell growth or activation. This is the first structural report of human PNP complexed with immucillin-H. The comparison of the complex HsPNP-ImmH with recent crystallographic structures of human PNP explains the high specificity of immucillin-H for human PNP.
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
1PF7 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Purine-nucleoside phosphorylase, with EC number 2.4.2.1 Full crystallographic information is available from OCA.
Reference
Structural basis for inhibition of human PNP by immucillin-H., Filgueira de Azevedo W Jr, Canduri F, Marangoni dos Santos D, Pereira JH, Dias MV, Silva RG, Mendes MA, Basso LA, Palma MS, Santos DS, Biochem Biophys Res Commun. 2003 Oct 3;309(4):917-22. PMID:13679061
Page seeded by OCA on Thu Feb 21 14:28:09 2008
Categories: Homo sapiens | Purine-nucleoside phosphorylase | Single protein | Basso, L A. | Canduri, F. | Dias, M V.B. | Jr., W F.De Azevedo. | Mendes, M A. | Palma, M S. | Pereira, J H. | Santos, D M.Dos. | Santos, D S. | Silva, R G. | IMH | SO4 | Crystallography | Drug design | Purine nucleoside phosphorylase | Synchrotron
