4gax: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal Structure of an alpha-Bisabolol synthase mutant== | |||
=== | <StructureSection load='4gax' size='340' side='right' caption='[[4gax]], [[Resolution|resolution]] 1.99Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4gax]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Artemisia_annua Artemisia annua]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GAX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GAX FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fjq|4fjq]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AaBOS, AMS1, KCS12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=35608 Artemisia annua])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Amorpha-4,11-diene_synthase Amorpha-4,11-diene synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.3.24 4.2.3.24] </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=4gax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gax OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gax RCSB], [http://www.ebi.ac.uk/pdbsum/4gax PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Most terpene synthases (TPSs) contain plasticity residues that are responsible for diversified terpene products and functional evolution, which provide a potential for improving catalytic efficiency. Artemisinin, a sesquiterpene lactone from Artemisia annua L., is widely used for malaria treatment and progress has been made in engineering the production of artemisinin or its precursors. Here, we report a new sesquiterpene synthase from A. annua, alpha-bisabolol synthase (AaBOS), which has high sequence identity to amorpha-4,11-diene synthase (AaADS), a key enzyme in artemisinin biosynthesis. Comparative analysis of the two enzymes by domain-swapping and structure-based mutagenesis led to the identification of several plasticity residues, whose alteration changed the product profile of AaBOS to include gamma-humulene as the major product. To elucidate the underlying mechanisms, we solved the crystal structures of AaBOS and a gamma-humulene-producing AaBOS mutant (AaBOS-M2). Among the plasticity residues, position 399, located in the substrate binding pocket, is crucial for both enzymes. In AaBOS, substitution of Leu with Thr (AaBOSL339T) is required for gamma-humulene production; whereas in AaADS, replacing the Thr with Ser (AaADST399S) resulted in a substantial increase of the activity of amorpha-4,11-diene production, likely as a result of accelerated product release. Our work demonstrates that substitution of plasticity residues holds a potential for improving catalytic efficiency of the enzyme. | |||
Rational engineering plasticity residues of sesquiterpene synthases from Artemisia annua: product specificity and catalytic efficiency.,Li JX, Fang X, Zhao Q, Ruan JX, Yang CQ, Wang LJ, Miller DJ, Faraldos JA, Allemann RK, Chen XY, Zhang P Biochem J. 2013 Feb 26. PMID:23438177<ref>PMID:23438177</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Amorpha-4,11-diene synthase]] | [[Category: Amorpha-4,11-diene synthase]] | ||
[[Category: Artemisia annua]] | [[Category: Artemisia annua]] | ||
[[Category: Li, J | [[Category: Li, J]] | ||
[[Category: Peng, Z | [[Category: Peng, Z]] | ||
[[Category: Lyase]] | [[Category: Lyase]] | ||
[[Category: Sesquiterpene synthase]] | [[Category: Sesquiterpene synthase]] | ||
