2on6: Difference between revisions

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-{{Seed}}
-[[Image:2on6.png|left|200px]]
-<!--
+==Crystal structure of human purine nucleoside phosphorylase mutant H257F with Imm-H==
-The line below this paragraph, containing "STRUCTURE_2on6", creates the "Structure Box" on the page.
+<StructureSection load='2on6' size='340' side='right'caption='[[2on6]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2on6]] 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=2ON6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ON6 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.503&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMH:1,4-DIDEOXY-4-AZA-1-(S)-(9-DEAZAHYPOXANTHIN-9-YL)-D-RIBITOL'>IMH</scene></td></tr>
-{{STRUCTURE_2on6|  PDB=2on6  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2on6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2on6 OCA], [https://pdbe.org/2on6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2on6 RCSB], [https://www.ebi.ac.uk/pdbsum/2on6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2on6 ProSAT]</span></td></tr>
+</table>
+== 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/on/2on6_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=2on6 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The X-ray crystal structures of human purine nucleoside phosphorylase (PNP) with bound inosine or transition-state analogues show His257 within hydrogen bonding distance of the 5'-hydroxyl. The mutants His257Phe, His257Gly, and His257Asp exhibited greatly decreased affinity for Immucillin-H (ImmH), binding this mimic of an early transition state as much as 370-fold (Km/Ki) less tightly than native PNP. In contrast, these mutants bound DADMe-ImmH, a mimic of a late transition state, nearly as well as the native enzyme. These results indicate that His257 serves an important role in the early stages of transition-state formation. Whereas mutation of His257 resulted in little variation in the PNP x DADMe-ImmH x SO4 structures, His257Phe x ImmH x PO4 showed distortion at the 5'-hydroxyl, indicating the importance of H-bonding in positioning this group during progression to the transition state. Binding isotope effect (BIE) and kinetic isotope effect (KIE) studies of the remote 5'-(3)H for the arsenolysis of inosine with native PNP revealed a BIE of 1.5% and an unexpectedly large intrinsic KIE of 4.6%. This result is interpreted as a moderate electronic distortion toward the transition state in the Michaelis complex with continued development of a similar distortion at the transition state. The mutants His257Phe, His257Gly, and His257Asp altered the 5'-(3)H intrinsic KIE to -3, -14, and 7%, respectively, while the BIEs contributed 2, 2, and -2%, respectively. These surprising results establish that forces in the Michaelis complex, reported by the BIEs, can be reversed or enhanced at the transition state.
-===Crystal stucture of human purine nucleoside phosphorylase mutant H257F with Imm-H===
+Neighboring group participation in the transition state of human purine nucleoside phosphorylase.,Murkin AS, Birck MR, Rinaldo-Matthis A, Shi W, Taylor EA, Almo SC, Schramm VL Biochemistry. 2007 May 1;46(17):5038-49. Epub 2007 Apr 4. PMID:17407325<ref>PMID:17407325</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2on6" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_17407325}}, adds the Publication Abstract to the page
+*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 17407325 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_17407325}}
+__TOC__
+</StructureSection>
-==About this Structure==
-ON6 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=2ON6 OCA].
-==Reference==
-Neighboring group participation in the transition state of human purine nucleoside phosphorylase., Murkin AS, Birck MR, Rinaldo-Matthis A, Shi W, Taylor EA, Almo SC, Schramm VL, Biochemistry. 2007 May 1;46(17):5038-49. Epub 2007 Apr 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17407325 17407325]
 [[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: Rinaldo-Matthis A]]
-[[Category: Rinaldo-Matthis, A.]]
+[[Category: Schramm VL]]
-[[Category: Schramm, V L.]]
-[[Category: Purine nucleoside phosphorylase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 12:38:08 2008''