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- | [[Image:3bgs.jpg|left|200px]] | |
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- | {{Structure
| + | ==Structure of human purine nucleoside phosphorylase with L-DADMe-ImmH and phosphate== |
- | |PDB= 3bgs |SIZE=350|CAPTION= <scene name='initialview01'>3bgs</scene>, resolution 2.099Å
| + | <StructureSection load='3bgs' size='340' side='right'caption='[[3bgs]], [[Resolution|resolution]] 2.10Å' scene=''> |
- | |SITE= <scene name='pdbsite=AC1:Po4+Binding+Site+For+Residue+A+302'>AC1</scene>, <scene name='pdbsite=AC2:Po4+Binding+Site+For+Residue+A+303'>AC2</scene>, <scene name='pdbsite=AC3:Po4+Binding+Site+For+Residue+A+304'>AC3</scene> and <scene name='pdbsite=AC4:Dih+Binding+Site+For+Residue+A+301'>AC4</scene>
| + | == Structural highlights == |
- | |LIGAND= <scene name='pdbligand=DIH:3-HYDROXY-4-HYDROXYMETHYL-1-(4-OXO-4,4A,5,7A-TETRAHYDRO-3H-PYRROLO[3,2-D]PYRIMIDIN-7-YLMETHYL)-PYRROLIDINIUM'>DIH</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>
| + | <table><tr><td colspan='2'>[[3bgs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BGS FirstGlance]. <br> |
- | |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>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.099Å</td></tr> |
- | |GENE= NP, PNP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DIH:3-HYDROXY-4-HYDROXYMETHYL-1-(4-OXO-4,4A,5,7A-TETRAHYDRO-3H-PYRROLO[3,2-D]PYRIMIDIN-7-YLMETHYL)-PYRROLIDINIUM'>DIH</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
- | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bgs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgs OCA], [https://pdbe.org/3bgs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bgs RCSB], [https://www.ebi.ac.uk/pdbsum/3bgs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bgs ProSAT]</span></td></tr> |
- | |RELATEDENTRY=[[1rr6|1RR6]], [[1rt9|1RT9]], [[1rsz|1RSZ]]
| + | </table> |
- | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bgs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgs OCA], [http://www.ebi.ac.uk/pdbsum/3bgs PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bgs RCSB]</span>
| + | == Disease == |
- | }}
| + | [https://www.uniprot.org/uniprot/PNPH_HUMAN PNPH_HUMAN] Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:[https://omim.org/entry/613179 613179]. It leads to a severe T-cell immunodeficiency with neurologic disorder in children.<ref>PMID:3029074</ref> <ref>PMID:1384322</ref> <ref>PMID:8931706</ref> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/PNPH_HUMAN 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.<ref>PMID:2104852</ref> |
| + | == Evolutionary Conservation == |
| + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> |
| + | <jmolCheckbox> |
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bg/3bgs_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| + | </jmolCheckbox> |
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bgs ConSurf]. |
| + | <div style="clear:both"></div> |
| + | <div style="background-color:#fffaf0;"> |
| + | == Publication Abstract from PubMed == |
| + | Human purine nucleoside phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP. |
| | | |
- | '''Structure of human purine nucleoside phosphorylase with L-DADMe-ImmH and phosphate'''
| + | L-Enantiomers of transition state analogue inhibitors bound to human purine nucleoside phosphorylase.,Rinaldo-Matthis A, Murkin AS, Ramagopal UA, Clinch K, Mee SP, Evans GB, Tyler PC, Furneaux RH, Almo SC, Schramm VL J Am Chem Soc. 2008 Jan 23;130(3):842-4. Epub 2007 Dec 23. PMID:18154341<ref>PMID:18154341</ref> |
| | | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> |
| + | <div class="pdbe-citations 3bgs" style="background-color:#fffaf0;"></div> |
| | | |
- | ==Overview== | + | ==See Also== |
- | Human purine nucleoside phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP.
| + | *[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]] |
- | | + | == References == |
- | ==About this Structure== | + | <references/> |
- | 3BGS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BGS OCA].
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==Reference==
| + | |
- | L-Enantiomers of transition state analogue inhibitors bound to human purine nucleoside phosphorylase., Rinaldo-Matthis A, Murkin AS, Ramagopal UA, Clinch K, Mee SP, Evans GB, Tyler PC, Furneaux RH, Almo SC, Schramm VL, J Am Chem Soc. 2008 Jan 23;130(3):842-4. Epub 2007 Dec 23. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18154341 18154341]
| + | |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
- | [[Category: Purine-nucleoside phosphorylase]] | + | [[Category: Large Structures]] |
- | [[Category: Single protein]]
| + | [[Category: Almo SC]] |
- | [[Category: Almo, S C.]] | + | [[Category: Murkin AS]] |
- | [[Category: Murkin, A S.]] | + | [[Category: Ramagopal UA]] |
- | [[Category: Ramagopal, U A.]] | + | [[Category: Schramm VL]] |
- | [[Category: Schramm, V L.]] | + | |
- | [[Category: l-enantiomer]]
| + | |
- | [[Category: pnp]]
| + | |
- | [[Category: transferase]]
| + | |
- | [[Category: transition state analogue]]
| + | |
- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:26:07 2008''
| + | |
| Structural highlights
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
Human purine nucleoside phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP.
L-Enantiomers of transition state analogue inhibitors bound to human purine nucleoside phosphorylase.,Rinaldo-Matthis A, Murkin AS, Ramagopal UA, Clinch K, Mee SP, Evans GB, Tyler PC, Furneaux RH, Almo SC, Schramm VL J Am Chem Soc. 2008 Jan 23;130(3):842-4. Epub 2007 Dec 23. PMID:18154341[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Rinaldo-Matthis A, Murkin AS, Ramagopal UA, Clinch K, Mee SP, Evans GB, Tyler PC, Furneaux RH, Almo SC, Schramm VL. L-Enantiomers of transition state analogue inhibitors bound to human purine nucleoside phosphorylase. J Am Chem Soc. 2008 Jan 23;130(3):842-4. Epub 2007 Dec 23. PMID:18154341 doi:10.1021/ja710733g
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