1ore: Difference between revisions

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-[[Image:1ore.gif|left|200px]]<br />
-<applet load="1ore" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1ore, resolution 2.10&Aring;" />
-'''Human Adenine Phosphoribosyltransferase'''<br />
-==Overview==
+==Human Adenine Phosphoribosyltransferase==
-In mammals, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) is, present in all tissues and provides the only known mechanism for the, metabolic salvage of adenine resulting from the polyamine biosynthesis, pathway or from dietary sources. In humans, APRT deficiency results in, serious kidney illness such as nephrolithiasis, interstitial nephritis, and chronic renal failure as a result of 2,8-dihydroxyadenine (DHA), precipitation in the renal interstitium. To address the molecular basis of, DHA-urolithiasis, the recombinant human APRT was crystallized in complex, with adenosine 5'-monophosphate (AMP). Refinement of X-ray diffraction, data extended to 2.1 A resolution led to a final crystallographic, R(factor) of 13.3% and an R(free) of 17.6%. This structure is composed of, nine beta-strands and six alpha-helices, and the active site pocket opens, slightly to accommodate the AMP product. The core of APRT is similar to, that of other phosphoribosyltransferases (PRTases), although the, adenine-binding domain is quite different. Structural comparisons between, the human APRT and other "type I" PRTases of known structure revealed, several important features of the biochemistry of PRTases. We propose that, the residues located at positions corresponding to Leu159 and Ala131 in, hAPRT are responsible for the base specificities of type I PRTases. The, comparative analysis shown here also provides structural information for, the mechanism by which mutations in the human APRT lead to, DHA-urolithiasis.
+<StructureSection load='1ore' size='340' side='right'caption='[[1ore]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1ore]] 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=1ORE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ORE FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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=1ore FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ore OCA], [https://pdbe.org/1ore PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ore RCSB], [https://www.ebi.ac.uk/pdbsum/1ore PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ore ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/APT_HUMAN APT_HUMAN] Defects in APRT are the cause of adenine phosphoribosyltransferase deficiency (APRTD) [MIM:[https://omim.org/entry/614723 614723]; also known as 2,8-dihydroxyadenine urolithiasis. An enzymatic deficiency that can lead to urolithiasis and renal failure. Patients have 2,8-dihydroxyadenine (DHA) urinary stones.<ref>PMID:1746557</ref> <ref>PMID:7915931</ref> <ref>PMID:3680503</ref> <ref>PMID:3343350</ref> <ref>PMID:1353080</ref> <ref>PMID:11243733</ref> <ref>PMID:15571218</ref> <ref>PMID:21635362</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/APT_HUMAN APT_HUMAN] Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.
+== 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/or/1ore_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=1ore ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-Known disease associated with this structure: Urolithiasis, 2,8-dihydroxyadenine OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=102600 102600]]
+*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-ORE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL and AMP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenine_phosphoribosyltransferase Adenine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.7 2.4.2.7] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ORE OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Three-dimensional structure of human adenine phosphoribosyltransferase and its relation to DHA-urolithiasis., Silva M, Silva CH, Iulek J, Thiemann OH, Biochemistry. 2004 Jun 22;43(24):7663-71. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15196008 15196008]
-[[Category: Adenine phosphoribosyltransferase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Iulek, J.]]
+[[Category: Iulek J]]
-[[Category: Oliva, G.]]
+[[Category: Oliva G]]
-[[Category: Silva, C.H.T.P.]]
+[[Category: Silva CHTP]]
-[[Category: Silva, M.]]
+[[Category: Silva M]]
-[[Category: Thiemann, O.H.]]
+[[Category: Thiemann OH]]
-[[Category: AMP]]
-[[Category: CL]]
-[[Category: glycosyl transferase]]
-[[Category: human adenine phosphoribosyltransferase]]
-[[Category: leishmaniasis]]
-[[Category: purine salvage]]
-[[Category: urolithiasis]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:35:51 2007''