1pwy

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|PDB= 1pwy |SIZE=350|CAPTION= <scene name='initialview01'>1pwy</scene>, resolution 2.80&Aring;
|PDB= 1pwy |SIZE=350|CAPTION= <scene name='initialview01'>1pwy</scene>, resolution 2.80&Aring;
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=AC2:9-HYROXYETHOXYMETHYLGUANINE'>AC2</scene>
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|LIGAND= <scene name='pdbligand=AC2:9-HYROXYETHOXYMETHYLGUANINE'>AC2</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= PNP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
|GENE= PNP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=
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|RELATEDENTRY=[[1m73|1M73]], [[1pf7|1PF7]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pwy OCA], [http://www.ebi.ac.uk/pdbsum/1pwy PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pwy RCSB]</span>
}}
}}
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==Overview==
==Overview==
In human, purine nucleoside phosphorylase (HsPNP) is responsible 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 has been submitted to extensive structure-based drug design. This work reports the first crystallographic study of human PNP complexed with acyclovir (HsPNP:Acy). Acyclovir is a potent clinically useful inhibitor of replicant herpes simplex virus that also inhibits human PNP but with a relatively lower inhibitory activity (K(i)=90 microM). Analysis of the structural differences among the HsPNP:Acy complex, PNP apoenzyme, and HsPNP:Immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design.
In human, purine nucleoside phosphorylase (HsPNP) is responsible 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 has been submitted to extensive structure-based drug design. This work reports the first crystallographic study of human PNP complexed with acyclovir (HsPNP:Acy). Acyclovir is a potent clinically useful inhibitor of replicant herpes simplex virus that also inhibits human PNP but with a relatively lower inhibitory activity (K(i)=90 microM). Analysis of the structural differences among the HsPNP:Acy complex, PNP apoenzyme, and HsPNP:Immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design.
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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: AC2]]
 
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[[Category: SO4]]
 
[[Category: acyclovir]]
[[Category: acyclovir]]
[[Category: crystallography]]
[[Category: crystallography]]
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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 13:30:06 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:05:43 2008''

Revision as of 20:05, 30 March 2008

Image:1pwy.jpg


PDB ID 1pwy

Drag the structure with the mouse to rotate
, resolution 2.80Å
Ligands: ,
Gene: PNP (Homo sapiens)
Activity: Purine-nucleoside phosphorylase, with EC number 2.4.2.1
Related: 1M73, 1PF7


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



CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH ACYCLOVIR


Overview

In human, purine nucleoside phosphorylase (HsPNP) is responsible 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 has been submitted to extensive structure-based drug design. This work reports the first crystallographic study of human PNP complexed with acyclovir (HsPNP:Acy). Acyclovir is a potent clinically useful inhibitor of replicant herpes simplex virus that also inhibits human PNP but with a relatively lower inhibitory activity (K(i)=90 microM). Analysis of the structural differences among the HsPNP:Acy complex, PNP apoenzyme, and HsPNP:Immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design.

About this Structure

1PWY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of human purine nucleoside phosphorylase complexed with acyclovir., dos Santos DM, Canduri F, Pereira JH, Vinicius Bertacine Dias M, Silva RG, Mendes MA, Palma MS, Basso LA, de Azevedo WF Jr, Santos DS, Biochem Biophys Res Commun. 2003 Aug 29;308(3):553-9. PMID:12914786

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