Top Level Name
⌊ Superfamily (core) Isoprenoid Synthase Type I
⌊ Subgroup Polyprenyl Transferase Like
⌊ Family octaprenyl pyrophosphate synthase
|Sequences of this family were last updated on Oct. 3, 2013|
Catalyzes the condensation of dimethylallyldiphosphate (DMAPP)or farnesyl diphosphate (FPP) and isopentenyl diphosphate (IPP) to yield octaprenyl diphosphate.
Wallrapp FH, Pan JJ, Ramamoorthy G, Almonacid DE, Hillerich BS, Seidel R, Patskovsky Y, Babbitt PC, Almo SC, Jacobson MP, Poulter CD
Prediction of function for the polyprenyl transferase subgroup in the isoprenoid synthase superfamily
The number of available protein sequences has increased exponentially with the advent of high-throughput genomic sequencing, creating a significant challenge for functional annotation. Here, we describe a large-scale study on assigning function to unknown members of the trans-polyprenyl transferase (E-PTS) subgroup in the isoprenoid synthase superfamily, which provides substrates for the biosynthesis of the more than 55,000 isoprenoid metabolites. Although the mechanism for determining the product chain length for these enzymes is known, there is no simple relationship between function and primary sequence, so that assigning function is challenging. We addressed this challenge through large-scale bioinformatics analysis of >5,000 putative polyprenyl transferases; experimental characterization of the chain-length specificity of 79 diverse members of this group; determination of 27 structures of 19 of these enzymes, including seven cocrystallized with substrate analogs or products; and the development and successful application of a computational approach to predict function that leverages available structural data through homology modeling and docking of possible products into the active site. The crystallographic structures and computational structural models of the enzyme-ligand complexes elucidate the structural basis of specificity. As a result of this study, the percentage of E-PTS sequences similar to functionally annotated ones (BLAST e-value ≤ 1e(-70)) increased from 40.6 to 68.8%, and the percentage of sequences similar to available crystal structures increased from 28.9 to 47.4%. The high accuracy of our blind prediction of newly characterized enzymes indicates the potential to predict function to the complete polyprenyl transferase subgroup of the isoprenoid synthase superfamily computationally.
Sequence Similarity Networks
Download a Sequence Similarity Network of this family (XGMML format ).
Network downloads are XGMML files that are readable by program such as Cytoscape. In these networks, nodes represent proteins and edges represent pairwise similarities better than a given E-value cutoff. Additionally, these networks contain several attributes with data from the SFLD.
|Download a Full Network based on||Full network (25-Oct-2013)|
A detailed list of included node attributes, their definitions, and their uses is available here [revised: 10/11/2013].
Multiple Sequence Alignment
Multiple Sequence Alignment
Download full-length sequence sets of this family as a FASTA format file.
Download annotation of sequences sets of this family as a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application.
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The maximum E-value at which pairwise similarities are included in the network.
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octaprenyl diphosphate synthase