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PMID: 20602361 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Diterpene cyclases and the nature of the isoprene fold.

Proteins ·Vol. 78 ·No. 11 ·2010-08-15 ·Pages 2417-32

Cao R, Zhang Y, Mann FM, Huang C, Mukkamala D, Hudock MP, Mead ME, Prisic S, Wang K, Lin FY, Chang TK, Peters RJ, Oldfield E

Abstract

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 approximately 20 alpha-helices and the same conserved "QW" and DxDD motifs as in triterpene cyclases, indicating the presence of a betagamma barrel structure. Plant diterpene cyclases have a similar catalytic motif and betagamma-domain structure together with a third, alpha-domain, forming an alphabetagamma structure, and in H(+)-initiated cyclases, there is an EDxxD-like Mg(2+)/diphosphate binding motif located in the gamma-domain. The results support a new view of terpene cyclase structure and function and suggest evolution from ancient (betagamma) bacterial triterpene cyclases to (betagamma) bacterial and thence to (alphabetagamma) plant diterpene cyclases.

MeSH Terms
Alkyl and Aryl Transferases/chemistry,metabolism Amino Acid Sequence Bacterial Proteins/chemistry,genetics,metabolism Binding Sites Butadienes/chemistry,metabolism Cluster Analysis Diterpenes/metabolism Evolution, Molecular Hemiterpenes/chemistry,metabolism Isomerases/chemistry,genetics,metabolism Magnesium/chemistry,metabolism Molecular Sequence Data Mutagenesis, Site-Directed Pentanes/chemistry,metabolism Plant Proteins/chemistry,genetics,metabolism Protein Structure, Tertiary Recombinant Fusion Proteins/chemistry,genetics,metabolism Sequence Alignment Structure-Activity Relationship
Chemicals
Bacterial Proteins Butadienes Diterpenes Hemiterpenes Pentanes Plant Proteins Recombinant Fusion Proteins isoprene Alkyl and Aryl Transferases Isomerases abietadiene cyclase Magnesium
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Cao Rong
Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Zhang Yonghui
Mann Francis M
Huang Cancan
Mukkamala Dushyant
Hudock Michael P
Mead Matthew E
Prisic Sladjana
Wang Ke
Lin Fu-Yang
Chang Ting-Kai
Peters Reuben J
Oldfield Eric
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Article Info
Journal
Proteins
Abbr.
Proteins
ISSN
1097-0134
DOI
10.1002/prot.22751
Published
2010-08-15
Pages
2417-32
Language
English
Region
United States
NLM ID
8700181
PMCID
PMC3805035
Subset
IM
Grants
NIGMS NIH HHS · R01 GM065307 · United States
NIGMS NIH HHS · R01 GM076324 · United States
NIGMS NIH HHS · GM076324 · United States
NIGMS NIH HHS · GM65307 · United States
External Links
PubMed source DOI: 10.1002/prot.22751 PMC Full Text View journal details
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