View source for 6axo


==F96S Epi-isozizaene synthase==
<StructureSection load='6axo' size='340' side='right'caption='[[6axo]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6axo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_coelicolor_A3(2) Streptomyces coelicolor A3(2)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AXO 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]] 2.1&#8491;</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=6axo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6axo OCA], [https://pdbe.org/6axo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6axo RCSB], [https://www.ebi.ac.uk/pdbsum/6axo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6axo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CYC1_STRCO CYC1_STRCO] Catalyzes the cyclization of farnesyl diphosphate (FPP) to the sesquiterpene epi-isozizaene.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The sesquiterpene cyclase epi-isozizaene synthase (EIZS) catalyzes the cyclization of farnesyl diphosphate to form the tricyclic hydrocarbon precursor of the antibiotic albaflavenone. The hydrophobic active site pocket of EIZS serves as a template as it binds and chaperones the flexible substrate and carbocation intermediates through the conformations required for a multistep reaction sequence. We previously demonstrated that the substitution of hydrophobic residues with other hydrophobic residues remolds the template and expands product chemodiversity [Li, R., Chou, W. K. W., Himmelberger, J. A., Litwin, K. M., Harris, G. G., Cane, D. E., and Christianson, D. W. (2014) Biochemistry 53, 1155-1168]. Here, we show that the substitution of hydrophobic residues-specifically, Y69, F95, F96, and W203-with polar side chains also yields functional enzyme catalysts that expand product chemodiversity. Fourteen new EIZS mutants are reported that generate product arrays in which eight new sesquiterpene products have been identified. Of note, some mutants generate acyclic and cyclic hydroxylated products, suggesting that the introduction of polarity in the hydrophobic pocket facilitates the binding of water capable of quenching carbocation intermediates. Furthermore, the substitution of polar residues for F96 yields high-fidelity sesquisabinene synthases. Crystal structures of selected mutants reveal that residues defining the three-dimensional contour of the hydrophobic pocket can be substituted without triggering significant structural changes elsewhere in the active site. Thus, more radical nonpolar-polar amino acid substitutions should be considered when terpenoid cyclase active sites are remolded by mutagenesis with the goal of exploring and expanding product chemodiversity.

Substitution of Aromatic Residues with Polar Residues in the Active Site Pocket of epi-Isozizaene Synthase Leads to the Generation of New Cyclic Sesquiterpenes.,Blank PN, Barrow GH, Chou WKW, Duan L, Cane DE, Christianson DW Biochemistry. 2017 Oct 17. doi: 10.1021/acs.biochem.7b00895. PMID:28967743<ref>PMID:28967743</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6axo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Barrow GH]]
[[Category: Blank PN]]
[[Category: Christianson DW]]