Diterpene cyclases and the nature of the isoprene fold |
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Authors: | Rong Cao Yonghui Zhang Francis M Mann Cancan Huang Dushyant Mukkamala Michael P Hudock Matthew E Mead Sladjana Prisic Ke Wang Fu‐Yang Lin Ting‐Kai Chang Reuben J Peters Eric Oldfield |
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Institution: | 1. Center for Biophysics and Computational Biology, University of Illinois at Urbana‐Champaign, Urbana, IL 61801;2. Rong Cao, Yonghui Zhang, and Francis M. Mann contributed equally to this work.;3. Department of Chemistry, University of Illinois at Urbana‐Champaign, Urbana, IL 61801;4. Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011 |
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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 ~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 Mg2+/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. |
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Keywords: | isoprenoid diterpene triterpene cyclase farnesyl diphosphate homology model |
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