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1pf7

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|PDB= 1pf7 |SIZE=350|CAPTION= <scene name='initialview01'>1pf7</scene>, resolution 2.60&Aring;
|PDB= 1pf7 |SIZE=350|CAPTION= <scene name='initialview01'>1pf7</scene>, resolution 2.60&Aring;
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=IMH:1,4-DIDEOXY-4-AZA-1-(S)-(9-DEAZAHYPOXANTHIN-9-YL)-D-RIBITOL'>IMH</scene>
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|LIGAND= <scene name='pdbligand=IMH:1,4-DIDEOXY-4-AZA-1-(S)-(9-DEAZAHYPOXANTHIN-9-YL)-D-RIBITOL'>IMH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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|ACTIVITY= [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]
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|ACTIVITY= <span class='plainlinks'>[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] </span>
|GENE=
|GENE=
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|DOMAIN=
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|RELATEDENTRY=[[1m73|1M73]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pf7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pf7 OCA], [http://www.ebi.ac.uk/pdbsum/1pf7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pf7 RCSB]</span>
}}
}}
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==Overview==
==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.
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.
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==Disease==
 
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Known diseases associated with this structure: Neutral lipid storage disease with myopathy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609059 609059]], Nucleoside phosphorylase deficiency, immunodeficiency due to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164050 164050]]
 
==About this Structure==
==About this Structure==
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[[Category: Santos, D S.]]
[[Category: Santos, D S.]]
[[Category: Silva, R G.]]
[[Category: Silva, R G.]]
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[[Category: IMH]]
 
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[[Category: SO4]]
 
[[Category: crystallography]]
[[Category: crystallography]]
[[Category: drug design]]
[[Category: drug design]]
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[[Category: synchrotron]]
[[Category: synchrotron]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:23:32 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:58:47 2008''

Revision as of 19:58, 30 March 2008


PDB ID 1pf7

Drag the structure with the mouse to rotate
, resolution 2.60Å
Ligands: ,
Activity: Purine-nucleoside phosphorylase, with EC number 2.4.2.1
Related: 1M73


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH IMMUCILLIN H


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.

About this Structure

1PF7 is a Single protein structure of sequence from Homo sapiens. 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

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