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Diterpene cyclases and the nature of the isoprene fold
Author(s) -
Cao Rong,
Zhang Yonghui,
Mann Francis M.,
Huang Cancan,
Mukkamala Dushyant,
Hudock Michael P.,
Mead Matthew E.,
Prisic Sladjana,
Wang Ke,
Lin FuYang,
Chang TingKai,
Peters Reuben J.,
Oldfield Eric
Publication year - 2010
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22751
Subject(s) - diterpene , terpene , stereochemistry , cyclase , chemistry , triterpene , biochemistry , structural motif , terpenoid , biology , enzyme , medicine , alternative medicine , pathology
The structures and mechanism of action of many terpene cyclases are known, but no structures of diterpene cyclases have yet been reported. Here, we propose structural models based on bioinformatics, site‐directed mutagenesis, domain swapping, enzyme inhibition, and spectroscopy that help explain the nature of diterpene cyclase structure, function, and evolution. Bacterial diterpene cyclases contain ∼20 α‐helices and the same conserved “QW” and DxDD motifs as in triterpene cyclases, indicating the presence of a βγ barrel structure. Plant diterpene cyclases have a similar catalytic motif and βγ‐domain structure together with a third, α‐domain, forming an αβγ structure, and in H + ‐initiated cyclases, there is an EDxxD‐like Mg 2+ /diphosphate binding motif located in the γ‐domain. The results support a new view of terpene cyclase structure and function and suggest evolution from ancient (βγ) bacterial triterpene cyclases to (βγ) bacterial and thence to (αβγ) plant diterpene cyclases. Proteins 2010. © 2010 Wiley‐Liss, Inc.