View source for 4la6


==Crystal structure of 2-methylisoborneol synthase from Streptomyces coelicolor A3(2) in complex with Mg2+ and 2-fluoroneryl diphosphate==
<StructureSection load='4la6' size='340' side='right'caption='[[4la6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4la6]] 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=4LA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LA6 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]] 2.001&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LA6:(2E)-2-FLUORO-3,7-DIMETHYLOCTA-2,6-DIEN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>LA6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4la6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4la6 OCA], [https://pdbe.org/4la6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4la6 RCSB], [https://www.ebi.ac.uk/pdbsum/4la6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4la6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MIBS_STRCO MIBS_STRCO] Catalyzes the cyclization of 2-methylgeranyl diphosphate (2-MeGPP) to 2-methylisoborneol (2-MIB), which likely involves the intermediacy of 2-methyllinalyl diphosphate. Is also able to catalyze the cyclization of geranyl diphosphate (GPP), albeit with much lower efficiency, leading to the formation of a complex mixture of cyclic monoterpenes, consisting of alpha-pinene (6%), beta-pinene (23%), limonene (32%), gamma-terpinene (29%), and delta-terpinene (10%).
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== Publication Abstract from PubMed ==
The crystal structure of 2-methylisoborneol synthase (MIBS) from Streptomyces coelicolor A3(2) has been determined in its unliganded state and in complex with two Mg2+ ions and 2-fluoroneryl diphosphate at 1.85 and 2.00 A resolution, respectively. Under normal circumstances, MIBS catalyzes the cyclization of the naturally occurring, noncanonical 11-carbon isoprenoid substrate, 2-methylgeranyl diphosphate, which first undergoes an ionization-isomerization-ionization sequence through the tertiary diphosphate intermediate 2-methyllinalyl diphosphate to enable subsequent cyclization chemistry. MIBS does not exhibit catalytic activity with 2-fluorogeranyl diphosphate, and we recently reported the crystal structure of MIBS complexed with this unreactive substrate analogue [ Koksal, M., Chou, W. K. W., Cane, D. E., Christianson, D. W. (2012) Biochemistry 51 , 3011-3020 ]. However, cocrystallization of MIBS with the fluorinated analogue of the tertiary allylic diphosphate intermediate, 2-fluorolinalyl diphosphate, reveals unexpected reactivity for the intermediate analogue and yields the crystal structure of the complex with the primary allylic diphosphate, 2-fluoroneryl diphosphate. Comparison with the structure of the unliganded enzyme reveals that the crystalline enzyme active site remains partially open, presumably due to the binding of only two Mg2+ ions. Assays in solution indicate that MIBS catalyzes the generation of (1R)-(+)-camphor from the substrate 2-fluorolinalyl diphosphate, suggesting that both 2-fluorolinalyl diphosphate and 2-methyllinalyl diphosphate follow the identical cyclization mechanism leading to 2-substituted isoborneol products; however, the initially generated 2-fluoroisoborneol cyclization product is unstable and undergoes elimination of hydrogen fluoride to yield (1R)-(+)-camphor.

Unexpected Reactivity of 2-Fluorolinalyl Diphosphate in the Active Site of Crystalline 2-Methylisoborneol Synthase.,Koksal M, Chou WK, Cane DE, Christianson DW Biochemistry. 2013 Jul 22. PMID:23844678<ref>PMID:23844678</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 4la6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Christianson DW]]
[[Category: Koksal M]]