1zn8
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='1zn8' size='340' side='right'caption='[[1zn8]], [[Resolution|resolution]] 1.76Å' scene=''> | <StructureSection load='1zn8' size='340' side='right'caption='[[1zn8]], [[Resolution|resolution]] 1.76Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1zn8]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1zn8]] is a 2 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=1ZN8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZN8 FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76Å</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=' | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zn8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zn8 OCA], [https://pdbe.org/1zn8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zn8 RCSB], [https://www.ebi.ac.uk/pdbsum/1zn8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zn8 ProSAT]</span></td></tr> |
| - | + | ||
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Disease == | == 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 == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 24: | Line 22: | ||
</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=1zn8 ConSurf]. | </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=1zn8 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Adenine phosphoribosyltransferase (APRT) is an important enzyme component of the purine recycling pathway. Parasitic protozoa of the order Kinetoplastida are unable to synthesize purines de novo and use the salvage pathway for the synthesis of purine bases rendering this biosynthetic pathway an attractive target for antiparasitic drug design. The recombinant human adenine phosphoribosyltransferase (hAPRT) structure was resolved in the presence of AMP in the active site to 1.76 A resolution and with the substrates PRPP and adenine simultaneously bound to the catalytic site to 1.83 A resolution. An additional structure was solved containing one subunit of the dimer in the apo-form to 2.10 A resolution. Comparisons of these three hAPRT structures with other 'type I' PRTases revealed several important features of this class of enzymes. Our data indicate that the flexible loop structure adopts an open conformation before and after binding of both substrates adenine and PRPP. Comparative analyses presented here provide structural evidence to propose the role of Glu104 as the residue that abstracts the proton of adenine N9 atom before its nucleophilic attack on the PRPP anomeric carbon. This work leads to new insights to the understanding of the APRT catalytic mechanism. | ||
| - | |||
| - | Structural Complexes of Human Adenine Phosphoribosyltransferase Reveal Novel Features of the APRT Catalytic Mechanism.,Silva CH, Silva M, Iulek J, Thiemann OH J Biomol Struct Dyn. 2008 Jun;25(6):589-98. PMID:18399692<ref>PMID:18399692</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1zn8" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| Line 40: | Line 29: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | + | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Iulek | + | [[Category: Iulek J]] |
| - | [[Category: Silva | + | [[Category: Silva M]] |
| - | [[Category: Thiemann | + | [[Category: Thiemann OH]] |
| - | [[Category: Tomich | + | [[Category: Tomich CHTP]] |
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
Human Adenine Phosphoribosyltransferase Complexed with AMP, in Space Group P1 at 1.76 A Resolution
| |||||||||||
