6M7F
Wild-type Cucumene Synthase
Summary for 6M7F
| Entry DOI | 10.2210/pdb6m7f/pdb |
| Descriptor | Cucumene Synthase (2 entities in total) |
| Functional Keywords | triquinane scaffold, open conformation, terpene cyclase, lyase |
| Biological source | Streptomyces clavuligerus (strain ATCC 27064 / DSM 738 / JCM 4710 / NBRC 13307 / NCIMB 12785 / NRRL 3585 / VKM Ac-602) |
| Total number of polymer chains | 4 |
| Total formula weight | 155049.81 |
| Authors | Blank, P.N.,Pemberton, T.A.,Christianson, D.W. (deposition date: 2018-08-20, release date: 2018-10-31, Last modification date: 2023-10-11) |
| Primary citation | Blank, P.N.,Pemberton, T.A.,Chow, J.Y.,Poulter, C.D.,Christianson, D.W. Crystal Structure of Cucumene Synthase, a Terpenoid Cyclase That Generates a Linear Triquinane Sesquiterpene. Biochemistry, 57:6326-6335, 2018 Cited by PubMed Abstract: Linear triquinanes are sesquiterpene natural products with hydrocarbon skeletons consisting of three fused five-membered rings. Importantly, several of these compounds exhibit useful anticancer, anti-inflammatory, and antibiotic properties. However, linear triquinanes pose significant challenges to organic synthesis because of the structural and stereochemical complexity of their hydrocarbon skeletons. To illuminate nature's solution to the generation of linear triquinanes, we now describe the crystal structure of Streptomyces clavuligerus cucumene synthase. This sesquiterpene cyclase catalyzes the stereospecific cyclization of farnesyl diphosphate to form a linear triquinane product, (5 S,7 S,10 R,11 S)-cucumene. Specifically, we report the structure of the wild-type enzyme at 3.05 Å resolution and the structure of the T181N variant at 1.96 Å resolution, both in the open active site conformations without any bound ligands. The high-resolution structure of T181N cucumene synthase enables inspection of the active site contour, which adopts a three-dimensional shape complementary to a linear triquinane. Several aromatic residues outline the active site contour and are believed to facilitate cation-π interactions that would stabilize carbocation intermediates in catalysis. Thus, aromatic residues in the active site not only define the template for catalysis but also play a role in reducing activation barriers in the multistep cyclization cascade. PubMed: 30346736DOI: 10.1021/acs.biochem.8b00899 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.051 Å) |
Structure validation
Download full validation report
