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1pwy

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Revision as of 18:39, 24 January 2018

CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH ACYCLOVIR

Structural highlights

1pwy is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1m73, 1pf7
Gene:	PNP (HUMAN)
Activity:	Purine-nucleoside phosphorylase, with EC number 2.4.2.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PNPH_HUMAN] Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:613179]. It leads to a severe T-cell immunodeficiency with neurologic disorder in children.^[1] ^[2] ^[3]

Function

[PNPH_HUMAN] The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Williams SR, Gekeler V, McIvor RS, Martin DW Jr. A human purine nucleoside phosphorylase deficiency caused by a single base change. J Biol Chem. 1987 Feb 15;262(5):2332-8. PMID:3029074
↑ Aust MR, Andrews LG, Barrett MJ, Norby-Slycord CJ, Markert ML. Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency. Am J Hum Genet. 1992 Oct;51(4):763-72. PMID:1384322
↑ Pannicke U, Tuchschmid P, Friedrich W, Bartram CR, Schwarz K. Two novel missense and frameshift mutations in exons 5 and 6 of the purine nucleoside phosphorylase (PNP) gene in a severe combined immunodeficiency (SCID) patient. Hum Genet. 1996 Dec;98(6):706-9. PMID:8931706
↑ Ealick SE, Rule SA, Carter DC, Greenhough TJ, Babu YS, Cook WJ, Habash J, Helliwell JR, Stoeckler JD, Parks RE Jr, et al.. Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution. J Biol Chem. 1990 Jan 25;265(3):1812-20. PMID:2104852
↑ 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. Crystal structure of human purine nucleoside phosphorylase complexed with acyclovir. Biochem Biophys Res Commun. 2003 Aug 29;308(3):553-9. PMID:12914786

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1pwy"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH ACYCLOVIR==
 <StructureSection load='1pwy' size='340' side='right' caption='[[1pwy]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PNP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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://pdbe.org/1pwy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pwy RCSB], [http://www.ebi.ac.uk/pdbsum/1pwy PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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://pdbe.org/1pwy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pwy RCSB], [http://www.ebi.ac.uk/pdbsum/1pwy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1pwy ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 17: / Line 18: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pw/1pwy_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pw/1pwy_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 32: / Line 33: @@
 </div>
 <div class="pdbe-citations 1pwy" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Purine nucleoside phosphorylase|Purine nucleoside phosphorylase]]
 == References ==
 <references/>

1pwy

From Proteopedia

Revision as of 18:39, 24 January 2018

CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH ACYCLOVIR

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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