View source for 5vjn


==Crystal Structure of Adenine Phosphoribosyltransferase from Saccharomyces cerevisiae Complexed with D-2,5-Dideoxy-2,5-Imino-Altritol 1,6-Bisphosphate (D-DIAB) and Adenine==
<StructureSection load='5vjn' size='340' side='right'caption='[[5vjn]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vjn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VJN 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]] 1.78&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADE:ADENINE'>ADE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IR8:[(2R,3S,4R,5R)-3,4-dihydroxypyrrolidine-2,5-diyl]bis(methylene)+bis[dihydrogen+(phosphate)]'>IR8</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=5vjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vjn OCA], [https://pdbe.org/5vjn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vjn RCSB], [https://www.ebi.ac.uk/pdbsum/5vjn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vjn ProSAT]</span></td></tr>
</table>
== Function ==
[https://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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5vjn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Almo SC]]
[[Category: Bonanno JB]]
[[Category: Ducati RG]]
[[Category: Harijan RK]]
[[Category: Schramm VL]]