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| - | [[Image:2isc.jpg|left|200px]] | |
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| - | {{Structure
| + | ==Crystal structure of Purine Nucleoside Phosphorylase from Trichomonas vaginalis with DADMe-Imm-A== |
| - | |PDB= 2isc |SIZE=350|CAPTION= <scene name='initialview01'>2isc</scene>, resolution 2.700Å
| + | <StructureSection load='2isc' size='340' side='right'caption='[[2isc]], [[Resolution|resolution]] 2.70Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=223:(3R,4R)-1-[(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL]-4-(HYDROXYMETHYL)PYRROLIDIN-3-OL'>223</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> | + | <table><tr><td colspan='2'>[[2isc]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Trichomonas_vaginalis Trichomonas vaginalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ISC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ISC 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]] 2.7Å</td></tr> |
| - | |GENE=
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=223:(3R,4R)-1-[(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL]-4-(HYDROXYMETHYL)PYRROLIDIN-3-OL'>223</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=2isc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2isc OCA], [https://pdbe.org/2isc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2isc RCSB], [https://www.ebi.ac.uk/pdbsum/2isc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2isc ProSAT]</span></td></tr> |
| - | |RELATEDENTRY=[[2i4t|2I4T]]
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2isc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2isc OCA], [http://www.ebi.ac.uk/pdbsum/2isc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2isc RCSB]</span>
| + | == Function == |
| - | }}
| + | [https://www.uniprot.org/uniprot/A2E7Y6_TRIV3 A2E7Y6_TRIV3] |
| | + | == 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/is/2isc_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=2isc ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''Crystal stucture of Purine Nucleoside Phosphorylase from Trichomonas vaginalis with DADMe-Imm-A'''
| + | ==See Also== |
| - | | + | *[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]] |
| - | | + | __TOC__ |
| - | ==Overview== | + | </StructureSection> |
| - | Trichomonas vaginalis is a parasitic protozoan purine auxotroph possessing a unique purine salvage pathway consisting of a bacterial type purine nucleoside phosphorylase (PNP) and a purine nucleoside kinase. Thus, T. vaginalis PNP (TvPNP) functions in the reverse direction relative to the PNPs in other organisms. Immucillin-A (ImmA) and DADMe-Immucillin-A (DADMe-ImmA) are transition state mimics of adenosine with geometric and electrostatic features that resemble early and late transition states of adenosine at the transition state stabilized by TvPNP. ImmA demonstrates slow-onset tight-binding inhibition with TvPNP, to give an equilibrium dissociation constant of 87 pM, an inhibitor release half-time of 17.2 min, and a Km/Kd ratio of 70,100. DADMe-ImmA resembles a late ribooxacarbenium ion transition state for TvPNP to give a dissociation constant of 30 pM, an inhibitor release half-time of 64 min, and a Km/Kd ratio of 203,300. The tight binding of DADMe-ImmA supports a late SN1 transition state. Despite their tight binding to TvPNP, ImmA and DADMe-ImmA are weak inhibitors of human and P. falciparum PNPs. The crystal structures of the TvPNP x ImmA x PO4 and TvPNP x DADMe-ImmA x PO4 ternary complexes differ from previous structures with substrate analogues. The tight binding with DADMe-ImmA is in part due to a 2.7 A ionic interaction between a PO4 oxygen and the N1' cation of the hydroxypyrrolidine and is weaker in the TvPNP x ImmA x PO4 structure at 3.5 A. However, the TvPNP x ImmA x PO4 structure includes hydrogen bonds between the 2'-hydroxyl and the protein that are not present in TvPNP x DADMe-ImmA x PO4. These structures explain why DADMe-ImmA binds tighter than ImmA. Immucillin-H is a 12 nM inhibitor of TvPNP but a 56 pM inhibitor of human PNP. And this difference is explained by isotope-edited difference infrared spectroscopy with [6-18O]ImmH to establish that O6 is the keto tautomer in TvPNP x ImmH x PO4, causing an unfavorable leaving-group interaction.
| + | [[Category: Large Structures]] |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | 2ISC is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Trichomonas_vaginalis Trichomonas vaginalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ISC OCA].
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| - | | + | |
| - | ==Reference==
| + | |
| - | Inhibition and structure of Trichomonas vaginalis purine nucleoside phosphorylase with picomolar transition state analogues., Rinaldo-Matthis A, Wing C, Ghanem M, Deng H, Wu P, Gupta A, Tyler PC, Evans GB, Furneaux RH, Almo SC, Wang CC, Schramm VL, Biochemistry. 2007 Jan 23;46(3):659-68. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17223688 17223688]
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| - | [[Category: Protein complex]] | + | |
| - | [[Category: Purine-nucleoside phosphorylase]]
| + | |
| | [[Category: Trichomonas vaginalis]] | | [[Category: Trichomonas vaginalis]] |
| - | [[Category: Almo, S C.]] | + | [[Category: Almo SC]] |
| - | [[Category: Rinaldo-Matthis, A.]] | + | [[Category: Rinaldo-Matthis A]] |
| - | [[Category: Schramm, V L.]] | + | [[Category: Schramm VL]] |
| - | [[Category: purine nucleoside phosphorylase]]
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| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:47:53 2008''
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