3pde: Difference between revisions
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== | ==Crystal structure of geranylgeranyl pyrophosphate synthase from Lactobacillus brevis atcc 367 complexed with isoprenyl diphosphate and magnesium== | ||
[[3pde]] is a 4 chain structure with sequence from [ | <StructureSection load='3pde' size='340' side='right'caption='[[3pde]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
[[ | == Structural highlights == | ||
[[ | <table><tr><td colspan='2'>[[3pde]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Levilactobacillus_brevis_ATCC_367 Levilactobacillus brevis ATCC 367]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PDE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PDE FirstGlance]. <br> | ||
[[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> | ||
[[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMA:DIMETHYLALLYL+DIPHOSPHATE'>DMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3pde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pde OCA], [https://pdbe.org/3pde PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pde RCSB], [https://www.ebi.ac.uk/pdbsum/3pde PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pde ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q03RR4_LEVBA Q03RR4_LEVBA] | |||
[[ | <div style="background-color:#fffaf0;"> | ||
[[ | == Publication Abstract from PubMed == | ||
[[Category: | 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. | ||
[[Category: | |||
[[Category: | Prediction of function for the polyprenyl transferase subgroup in the isoprenoid synthase superfamily.,Wallrapp FH, Pan JJ, Ramamoorthy G, Almonacid DE, Hillerich BS, Seidel R, Patskovsky Y, Babbitt PC, Almo SC, Jacobson MP, Poulter CD Proc Natl Acad Sci U S A. 2013 Mar 14. PMID:23493556<ref>PMID:23493556</ref> | ||
[[Category: | |||
[[Category: | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 3pde" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Farnesyl diphosphate synthase 3D structures|Farnesyl diphosphate synthase 3D structures]] | ||
*[[Geranylgeranyl pyrophosphate synthase 3D structures|Geranylgeranyl pyrophosphate synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Levilactobacillus brevis ATCC 367]] | |||
[[Category: Almo SC]] | |||
[[Category: Burley SK]] | |||
[[Category: Gerlt JA]] | |||
[[Category: Patskovsky Y]] | |||
[[Category: Poulter CD]] | |||
[[Category: Rutter M]] | |||
[[Category: Sauder JM]] | |||
[[Category: Toro R]] | |||
Latest revision as of 12:51, 6 September 2023
Crystal structure of geranylgeranyl pyrophosphate synthase from Lactobacillus brevis atcc 367 complexed with isoprenyl diphosphate and magnesiumCrystal structure of geranylgeranyl pyrophosphate synthase from Lactobacillus brevis atcc 367 complexed with isoprenyl diphosphate and magnesium
Structural highlights
FunctionPublication Abstract from PubMedThe 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. Prediction of function for the polyprenyl transferase subgroup in the isoprenoid synthase superfamily.,Wallrapp FH, Pan JJ, Ramamoorthy G, Almonacid DE, Hillerich BS, Seidel R, Patskovsky Y, Babbitt PC, Almo SC, Jacobson MP, Poulter CD Proc Natl Acad Sci U S A. 2013 Mar 14. PMID:23493556[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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