4MC8

Hedycaryol synthase in complex with HEPES

Summary for 4MC8

• Entry DOI: 10.2210/pdb4mc8/pdb
• Related: 1HM4 4MC0 4MC3
• Descriptor: Putative sesquiterpene cyclase, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID (3 entities in total)
• Functional Keywords: cyclase, terpenoid, terpene alpha domain class i, helix break, helix dipol, lyase
• Biological source: Kitasatospora setae
• Total number of polymer chains: 1
• Total formula weight: 38939.78

Authors

Baer, P.,Rabe, P.,Cirton, C.,Oliveira Mann, C.,Kaufmann, N.,Groll, M.,Dickschat, J. (deposition date: 2013-08-21, release date: 2014-01-29, Last modification date: 2023-09-20)

Primary citation

Baer, P.,Rabe, P.,Citron, C.A.,de Oliveira Mann, C.C.,Kaufmann, N.,Groll, M.,Dickschat, J.S.
Hedycaryol synthase in complex with nerolidol reveals terpene cyclase mechanism.
Chembiochem, 15:213-216, 2014

PubMed Abstract: The biosynthesis of terpenes is catalysed by class I and II terpene cyclases. Here we present structural data from a class I hedycaryol synthase in complex with nerolidol, serving as a surrogate for the reaction intermediate nerolidyl diphosphate. This prefolded ligand allows mapping of the active site and hence the identification of a key carbonyl oxygen of Val179, a highly conserved helix break (G1/2) and its corresponding helix dipole. Stabilising the carbocation at the substrate's C1 position, these elements act in concert to catalyse the 1,10 ring closure, thereby exclusively generating the anti-Markovnikov product. The delineation of a general mechanistic scaffold was confirmed by site-specific mutations. This work serves as a basis for understanding carbocation chemistry in enzymatic reactions and should contribute to future application of these enzymes in organic synthesis.

PubMed: 24399794
DOI: 10.1002/cbic.201300708

Experimental method

X-RAY DIFFRACTION (1.9 Å)