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4la6

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Revision as of 22:53, 24 December 2014

Crystal structure of 2-methylisoborneol synthase from Streptomyces coelicolor A3(2) in complex with Mg2+ and 2-fluoroneryl diphosphate

Structural highlights

4la6 is a 1 chain structure with sequence from Strco. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3v1v, 3v1x, 4la5
Gene:	SC1A4.08, SCBAC12C8.01, SCO7700 (STRCO)
Activity:	2-methylisoborneol synthase, with EC number 4.2.3.118
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[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%).

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Koksal M, Chou WK, Cane DE, Christianson DW. Unexpected Reactivity of 2-Fluorolinalyl Diphosphate in the Active Site of Crystalline 2-Methylisoborneol Synthase. Biochemistry. 2013 Jul 22. PMID:23844678 doi:10.1021/bi400797c

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4la6"

@@ Line 9: / Line 9: @@
 <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=4la6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4la6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4la6 RCSB], [http://www.ebi.ac.uk/pdbsum/4la6 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://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%).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4la6

From Proteopedia

Revision as of 22:53, 24 December 2014

Crystal structure of 2-methylisoborneol synthase from Streptomyces coelicolor A3(2) in complex with Mg2+ and 2-fluoroneryl diphosphate

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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