1yry: Difference between revisions

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New page: left|200px<br /> <applet load="1yry" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yry, resolution 2.80Å" /> '''Crystal structure o...
 
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[[Image:1yry.gif|left|200px]]<br />
[[Image:1yry.gif|left|200px]]<br /><applet load="1yry" size="350" color="white" frame="true" align="right" spinBox="true"  
<applet load="1yry" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="1yry, resolution 2.80&Aring;" />
caption="1yry, resolution 2.80&Aring;" />
'''Crystal structure of human PNP complexed with MESG'''<br />
'''Crystal structure of human PNP complexed with MESG'''<br />


==Overview==
==Overview==
Purine nucleoside phosphorylase (PNP) catalyzes the reversible, phosphorolysis of nucleosides and deoxynucleosides, generating ribose, 1-phosphate and the purine base, which is an important step of purine, catabolism pathway. The lack of such an activity in humans, owing to a, genetic disorder, causes T-cell impairment, and drugs that inhibit this, enzyme may have the potential of being utilized as modulators of the, immunological system to treat leukemia, autoimmune diseases, and rejection, in organ transplantation. Here, we describe kinetics and crystal structure, of human PNP in complex with 7-methyl-6-thio-guanosine, a synthetic, substrate, which is largely used in activity assays. Analysis of the, structure identifies different protein conformational changes upon ligand, binding, and comparison of kinetic and structural data permits an, understanding of the effects of atomic substitution on key positions of, the synthetic substrate and their consequences to enzyme binding and, catalysis. Such knowledge may be helpful in designing new PNP inhibitors.
Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and drugs that inhibit this enzyme may have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Here, we describe kinetics and crystal structure of human PNP in complex with 7-methyl-6-thio-guanosine, a synthetic substrate, which is largely used in activity assays. Analysis of the structure identifies different protein conformational changes upon ligand binding, and comparison of kinetic and structural data permits an understanding of the effects of atomic substitution on key positions of the synthetic substrate and their consequences to enzyme binding and catalysis. Such knowledge may be helpful in designing new PNP inhibitors.


==Disease==
==Disease==
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==About this Structure==
==About this Structure==
1YRY 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 MSG 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YRY OCA].  
1YRY 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=MSG:'>MSG</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=1YRY OCA].  


==Reference==
==Reference==
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[[Category: Purine-nucleoside phosphorylase]]
[[Category: Purine-nucleoside phosphorylase]]
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Basso, L.A.]]
[[Category: Basso, L A.]]
[[Category: Canduri, F.]]
[[Category: Canduri, F.]]
[[Category: Jr., W.F.de.Azevedo.]]
[[Category: Jr., W F.de Azevedo.]]
[[Category: Pereira, J.H.]]
[[Category: Pereira, J H.]]
[[Category: Santos, D.S.]]
[[Category: Santos, D S.]]
[[Category: Silva, R.G.]]
[[Category: Silva, R G.]]
[[Category: MSG]]
[[Category: MSG]]
[[Category: SO4]]
[[Category: SO4]]
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[[Category: synchrotron]]
[[Category: synchrotron]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:24:00 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:08:29 2008''