1ulb: Difference between revisions

Revision as of 07:34, 28 March 2018

APPLICATION OF CRYSTALLOGRAPHIC AND MODELING METHODS IN THE DESIGN OF PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITORS

Structural highlights

1ulb 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:	GUN, SO4
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

Competitive inhibitors of the salvage pathway enzyme purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) have been designed by using the three-dimensional structure of the enzyme as determined by x-ray crystallography. The process was an iterative one that utilized interactive computer graphics, Monte Carlo-based conformational searching, energy minimization, and x-ray crystallography. The proposed compounds were synthesized and tested by an in vitro assay. Among the compounds designed and synthesized are the most potent competitive inhibitors of purine nucleoside phosphorylase thus far reported.

Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors.,Ealick SE, Babu YS, Bugg CE, Erion MD, Guida WC, Montgomery JA, Secrist JA 3rd Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11540-4. PMID:1763067^[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
↑ Ealick SE, Babu YS, Bugg CE, Erion MD, Guida WC, Montgomery JA, Secrist JA 3rd. Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11540-4. PMID:1763067

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] Ealick SE, Babu YS, Bugg CE, Erion MD, Guida WC, Montgomery JA, Secrist JA 3rd. Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11540-4. PMID:1763067

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@@ Line 1: / Line 1: @@
 ==APPLICATION OF CRYSTALLOGRAPHIC AND MODELING METHODS IN THE DESIGN OF PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITORS==
 <StructureSection load='1ulb' size='340' side='right' caption='[[1ulb]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GUN:GUANINE'>GUN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1ulb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ulb OCA], [http://pdbe.org/1ulb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ulb RCSB], [http://www.ebi.ac.uk/pdbsum/1ulb 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=1ulb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ulb OCA], [http://pdbe.org/1ulb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ulb RCSB], [http://www.ebi.ac.uk/pdbsum/1ulb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ulb ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
    <jmolCheckbox>
-     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ul/1ulb_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ul/1ulb_consurf.spt"</scriptWhenChecked>
      <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>

1ulb: Difference between revisions

Revision as of 07:34, 28 March 2018

APPLICATION OF CRYSTALLOGRAPHIC AND MODELING METHODS IN THE DESIGN OF PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITORS

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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