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| | ==Crystal structure of purine nucleoside phosphorylase (E258D, L261A) mutant from human complexed with DADMe-ImmG and phosphate== | | ==Crystal structure of purine nucleoside phosphorylase (E258D, L261A) mutant from human complexed with DADMe-ImmG and phosphate== |
| - | <StructureSection load='5etj' size='340' side='right' caption='[[5etj]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='5etj' size='340' side='right'caption='[[5etj]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5etj]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ETJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ETJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5etj]] is a 6 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=5ETJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ETJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IM5:2-AMINO-7-{[(3R,4R)-3-HYDROXY-4-(HYDROXYMETHYL)PYRROLIDIN-1-YL]METHYL}-3,5-DIHYDRO-4H-PYRROLO[3,2-D]PYRIMIDIN-4-ONE'>IM5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3phb|3phb]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IM5:2-AMINO-7-{[(3R,4R)-3-HYDROXY-4-(HYDROXYMETHYL)PYRROLIDIN-1-YL]METHYL}-3,5-DIHYDRO-4H-PYRROLO[3,2-D]PYRIMIDIN-4-ONE'>IM5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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'>[https://proteopedia.org/fgij/fg.htm?mol=5etj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5etj OCA], [https://pdbe.org/5etj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5etj RCSB], [https://www.ebi.ac.uk/pdbsum/5etj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5etj ProSAT]</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=5etj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5etj OCA], [http://pdbe.org/5etj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5etj RCSB], [http://www.ebi.ac.uk/pdbsum/5etj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5etj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PNPH_HUMAN PNPH_HUMAN]] Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:[http://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> | + | [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 == | | == Function == |
| - | [[http://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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5etj" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5etj" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Purine-nucleoside phosphorylase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Almo, S C]] | + | [[Category: Large Structures]] |
| - | [[Category: Cameron, S A]] | + | [[Category: Almo SC]] |
| - | [[Category: Schramm, V L]] | + | [[Category: Cameron SA]] |
| - | [[Category: Suarez, J]] | + | [[Category: Schramm VL]] |
| - | [[Category: Phosphorylase]] | + | [[Category: Suarez J]] |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| 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]
Publication Abstract from PubMed
The relevance of sub-picosecond protein motions to the catalytic event remains a topic of debate. Heavy enzymes (isotopically substituted) provide an experimental tool for bond-vibrational links to enzyme catalysis. A recent transition path sampling study with heavy purine nucleoside phosphorylase (PNP) characterized the experimentally observed mass-dependent slowing of barrier crossing (Antoniou, D.; Ge, X.; Schramm, V. L.; Schwartz, S. D. J. Phys. Chem. Lett. 2012, 3, 3538). Here we computationally identify second-sphere amino acid residues predicted to influence the freedom of the catalytic site vibrational modes linked to heavy enzyme effects in PNP. We mutated heavy and light PNPs to increase the catalytic site vibrational freedom. Enzymatic barrier-crossing rates were converted from mass-dependent to mass-independent as a result of the mutations. The mutagenic uncoupling of femtosecond motions between catalytic site groups and reactants decreased transition state barrier crossing by 2 orders of magnitude, an indication of the femtosecond dynamic contributions to catalysis.
Modulating Enzyme Catalysis through Mutations Designed to Alter Rapid Protein Dynamics.,Zoi I, Suarez J, Antoniou D, Cameron SA, Schramm VL, Schwartz SD J Am Chem Soc. 2016 Mar 16;138(10):3403-9. doi: 10.1021/jacs.5b12551. Epub 2016, Mar 8. PMID:26927977[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
- ↑ Zoi I, Suarez J, Antoniou D, Cameron SA, Schramm VL, Schwartz SD. Modulating Enzyme Catalysis through Mutations Designed to Alter Rapid Protein Dynamics. J Am Chem Soc. 2016 Mar 16;138(10):3403-9. doi: 10.1021/jacs.5b12551. Epub 2016, Mar 8. PMID:26927977 doi:http://dx.doi.org/10.1021/jacs.5b12551
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