4lrd

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{{STRUCTURE_4lrd| PDB=4lrd | SCENE= }}
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==Phosphopentomutase 4H11 variant==
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===Phosphopentomutase 4H11 variant===
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<StructureSection load='4lrd' size='340' side='right' caption='[[4lrd]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24657930}}
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== Structural highlights ==
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[[4lrd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_14579 Atcc 14579]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LRD OCA]. <br>
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<b>Related:</b> [[3un3|3un3]], [[3tx0|3tx0]], [[3twz|3twz]], [[3m8z|3m8z]], [[4lr7|4lr7]], [[4lr8|4lr8]], [[4lr9|4lr9]], [[4lra|4lra]], [[4lrb|4lrb]], [[4lrc|4lrc]], [[4lre|4lre]], [[4lrf|4lrf]]<br>
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<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br>
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== Publication Abstract from PubMed ==
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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.
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==Function==
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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>
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[[http://www.uniprot.org/uniprot/DEOB_BACCR DEOB_BACCR]] Phosphotransfer between the C1 and C5 carbon atoms of pentose (By similarity).
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==About this Structure==
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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[[4lrd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_14579 Atcc 14579]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LRD OCA].
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== References ==
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<references/>
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==Reference==
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__TOC__
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<ref group="xtra">PMID:024657930</ref><references group="xtra"/><references/>
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</StructureSection>
[[Category: Atcc 14579]]
[[Category: Atcc 14579]]
[[Category: Phosphopentomutase]]
[[Category: Phosphopentomutase]]

Revision as of 05:34, 30 April 2014

Phosphopentomutase 4H11 variant

4lrd, resolution 1.78Å

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