View source for 4lr8


==Phosphopentomutase S154A variant soaked with ribose 5-phosphate==
<StructureSection load='4lr8' size='340' side='right'caption='[[4lr8]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4lr8]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_cereus Bacillus cereus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LR8 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=HSX:5-O-PHOSPHONO-ALPHA-D-RIBOFURANOSE'>HSX</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=4lr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lr8 OCA], [https://pdbe.org/4lr8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lr8 RCSB], [https://www.ebi.ac.uk/pdbsum/4lr8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lr8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DEOB_BACCR DEOB_BACCR] Phosphotransfer between the C1 and C5 carbon atoms of pentose (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Concatenation of engineered biocatalysts into multistep pathways markedly increases their utility, but the development of generalizable assembly methods remains a major challenge. Herein we evaluate 'bioretrosynthesis', which is an application of the retrograde evolution hypothesis, for biosynthetic pathway construction. To test bioretrosynthesis, we engineered a pathway for synthesis of the antiretroviral nucleoside analog didanosine (2',3'-dideoxyinosine). Applying both directed evolution- and structure-based approaches, we began pathway construction with a retro-extension from an engineered purine nucleoside phosphorylase and evolved 1,5-phosphopentomutase to accept the substrate 2,3-dideoxyribose 5-phosphate with a 700-fold change in substrate selectivity and threefold increased turnover in cell lysate. A subsequent retrograde pathway extension, via ribokinase engineering, resulted in a didanosine pathway with a 9,500-fold change in nucleoside production selectivity and 50-fold increase in didanosine production. Unexpectedly, the result of this bioretrosynthetic step was not a retro-extension from phosphopentomutase but rather the discovery of a fortuitous pathway-shortening bypass via the engineered ribokinase.

Bioretrosynthetic construction of a didanosine biosynthetic pathway.,Birmingham WR, Starbird CA, Panosian TD, Nannemann DP, Iverson TM, Bachmann BO Nat Chem Biol. 2014 Mar 23. doi: 10.1038/nchembio.1494. PMID:24657930<ref>PMID:24657930</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4lr8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus cereus]]
[[Category: Large Structures]]
[[Category: Bachmann BO]]
[[Category: Birmingham WA]]
[[Category: Iverson TM]]
[[Category: Nannemann DP]]
[[Category: Panosian TD]]
[[Category: Starbird CA]]