5vjp: Difference between revisions

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'''Unreleased structure'''


The entry 5vjp is ON HOLD until Paper Publication
==Crystal Structure of Adenine Phosphoribosyltransferase from Saccharomyces cerevisiae Complexed with L-2,5-Dideoxy-2,5-Imino-Altritol 1,6-Bisphosphate (L-DIAB) and Adenine==
<StructureSection load='5vjp' size='340' side='right' caption='[[5vjp]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vjp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VJP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VJP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADE:ADENINE'>ADE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IR9:[(2S,3R,4S,5S)-3,4-dihydroxypyrrolidine-2,5-diyl]bis(methylene)+bis[dihydrogen+(phosphate)]'>IR9</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vjn|5vjn]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=5vjp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vjp OCA], [http://pdbe.org/5vjp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vjp RCSB], [http://www.ebi.ac.uk/pdbsum/5vjp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vjp ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/APT1_YEAST APT1_YEAST]] Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.<ref>PMID:9864350</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Phosphoribosyl transferases (PRTs) are essential in nucleotide synthesis and salvage, amino acid, and vitamin synthesis. Transition state analysis of several PRTs has demonstrated ribocation-like transition states with a partial positive charge residing on the pentose ring. Core chemistry for synthesis of transition state analogues related to the 5-phospho-alpha-d-ribosyl 1-pyrophosphate (PRPP) reactant of these enzymes could be developed by stereospecific placement of bis-phosphate groups on an iminoaltritol ring. Cationic character is provided by the imino group and the bis-phosphates anchor both the 1- and 5-phosphate binding sites. We provide a facile synthetic path to these molecules. Cyclic-nitrone redox methodology was applied to the stereocontrolled synthesis of three stereoisomers of a selectively monoprotected diol relevant to the synthesis of transition-state analogue inhibitors. These polyhydroxylated pyrrolidine natural product analogues were bis-phosphorylated to generate analogues of the ribocationic form of 5-phosphoribosyl 1-phosphate. A safe, high yielding synthesis of the key intermediate represents a new route to these transition state mimics. An enantiomeric pair of iminoaltritol bis-phosphates (L-DIAB and D-DIAB) was prepared and shown to display inhibition of Plasmodium falciparum orotate phosphoribosyltransferase and Saccharomyces cerevisiae adenine phosphoribosyltransferase (ScAPRT). Crystallographic inhibitor binding analysis of L- and D-DIAB bound to the catalytic sites of ScAPRT demonstrates accommodation of both enantiomers by altered ring geometry and bis-phosphate catalytic site contacts.


Authors: Harijan, R.K., Ducati, R.G., Bonanno, J.B., Almo, S.C., Schramm, V.L.
Synthesis of bis-Phosphate Iminoaltritol Enantiomers and Structural Characterization with Adenine Phosphoribosyltransferase.,Harris LD, Harijan RK, Ducati RG, Evans GB, Hirsch BM, Schramm VL ACS Chem Biol. 2017 Dec 14. doi: 10.1021/acschembio.7b00601. PMID:29178779<ref>PMID:29178779</ref>


Description: Crystal Structure of Adenine Phosphoribosyltransferase from Saccharomyces cerevisiae Complexed with L-2,5-Dideoxy-2,5-Imino-Altritol 1,6-Bisphosphate (L-DIAB) and Adenine
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Almo, S.C]]
<div class="pdbe-citations 5vjp" style="background-color:#fffaf0;"></div>
[[Category: Schramm, V.L]]
== References ==
[[Category: Harijan, R.K]]
<references/>
[[Category: Bonanno, J.B]]
__TOC__
[[Category: Ducati, R.G]]
</StructureSection>
[[Category: Adenine phosphoribosyltransferase]]
[[Category: Almo, S C]]
[[Category: Bonanno, J B]]
[[Category: Ducati, R G]]
[[Category: Harijan, R K]]
[[Category: Schramm, V L]]
[[Category: 5-dideoxy-2]]
[[Category: 5-imino-altritol-1]]
[[Category: 6-bisphosphate]]
[[Category: L-2]]
[[Category: L-diab]]
[[Category: Transferase-transferase inhibitor complex]]
[[Category: Transition state analogue]]