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Genome-Wide Search for Eliminylating Domains Reveals Novel Function for BLES03-Like Proteins

Bacterial phosphothreonine lyases catalyze a novel posttranslational modification involving formation of dehydrobutyrine/dehyroalanine by β elimination of the phosphate group of phosphothreonine or phosphoserine residues in their substrate proteins. Though there is experimental evidence for presence...

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Autores principales: Khater, Shradha, Mohanty, Debasisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159009/
https://www.ncbi.nlm.nih.gov/pubmed/25062915
http://dx.doi.org/10.1093/gbe/evu161
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author Khater, Shradha
Mohanty, Debasisa
author_facet Khater, Shradha
Mohanty, Debasisa
author_sort Khater, Shradha
collection PubMed
description Bacterial phosphothreonine lyases catalyze a novel posttranslational modification involving formation of dehydrobutyrine/dehyroalanine by β elimination of the phosphate group of phosphothreonine or phosphoserine residues in their substrate proteins. Though there is experimental evidence for presence of dehydro amino acids in human proteins, no eukaryotic homologs of these lyases have been identified as of today. A comprehensive genome-wide search for identifying phosphothreonine lyase homologs in eukaryotes was carried out. Our fold-based search revealed structural and catalytic site similarity between bacterial phosphothreonine lyases and BLES03 (basophilic leukemia-expressed protein 03), a human protein with unknown function. Ligand induced conformational changes similar to bacterial phosphothreonine lyases, and movement of crucial arginines in the loop region to the catalytic pocket upon binding of phosphothreonine-containing peptides was seen during docking and molecular dynamics studies. Genome-wide search for BLES03 homologs using sensitive profile-based methods revealed their presence not only in eukaryotic classes such as chordata and fungi but also in bacterial and archaebacterial classes. The synteny of these archaebacterial BLES03-like proteins was remarkably similar to that of type IV lantibiotic synthetases which harbor LanL-like phosphothreonine lyase domains. Hence, context-based analysis reinforced our earlier sequence/structure-based prediction of phosphothreonine lyase catalytic function for BLES03. Our in silico analysis has revealed that BLES03-like proteins with previously unknown function are novel eukaryotic phosphothreonine lyases involved in biosynthesis of dehydro amino acids, whereas their bacterial and archaebacterial counterparts might be involved in biosynthesis of natural products similar to lantibiotics.
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spelling pubmed-41590092014-09-10 Genome-Wide Search for Eliminylating Domains Reveals Novel Function for BLES03-Like Proteins Khater, Shradha Mohanty, Debasisa Genome Biol Evol Research Article Bacterial phosphothreonine lyases catalyze a novel posttranslational modification involving formation of dehydrobutyrine/dehyroalanine by β elimination of the phosphate group of phosphothreonine or phosphoserine residues in their substrate proteins. Though there is experimental evidence for presence of dehydro amino acids in human proteins, no eukaryotic homologs of these lyases have been identified as of today. A comprehensive genome-wide search for identifying phosphothreonine lyase homologs in eukaryotes was carried out. Our fold-based search revealed structural and catalytic site similarity between bacterial phosphothreonine lyases and BLES03 (basophilic leukemia-expressed protein 03), a human protein with unknown function. Ligand induced conformational changes similar to bacterial phosphothreonine lyases, and movement of crucial arginines in the loop region to the catalytic pocket upon binding of phosphothreonine-containing peptides was seen during docking and molecular dynamics studies. Genome-wide search for BLES03 homologs using sensitive profile-based methods revealed their presence not only in eukaryotic classes such as chordata and fungi but also in bacterial and archaebacterial classes. The synteny of these archaebacterial BLES03-like proteins was remarkably similar to that of type IV lantibiotic synthetases which harbor LanL-like phosphothreonine lyase domains. Hence, context-based analysis reinforced our earlier sequence/structure-based prediction of phosphothreonine lyase catalytic function for BLES03. Our in silico analysis has revealed that BLES03-like proteins with previously unknown function are novel eukaryotic phosphothreonine lyases involved in biosynthesis of dehydro amino acids, whereas their bacterial and archaebacterial counterparts might be involved in biosynthesis of natural products similar to lantibiotics. Oxford University Press 2014-07-24 /pmc/articles/PMC4159009/ /pubmed/25062915 http://dx.doi.org/10.1093/gbe/evu161 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Khater, Shradha
Mohanty, Debasisa
Genome-Wide Search for Eliminylating Domains Reveals Novel Function for BLES03-Like Proteins
title Genome-Wide Search for Eliminylating Domains Reveals Novel Function for BLES03-Like Proteins
title_full Genome-Wide Search for Eliminylating Domains Reveals Novel Function for BLES03-Like Proteins
title_fullStr Genome-Wide Search for Eliminylating Domains Reveals Novel Function for BLES03-Like Proteins
title_full_unstemmed Genome-Wide Search for Eliminylating Domains Reveals Novel Function for BLES03-Like Proteins
title_short Genome-Wide Search for Eliminylating Domains Reveals Novel Function for BLES03-Like Proteins
title_sort genome-wide search for eliminylating domains reveals novel function for bles03-like proteins
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159009/
https://www.ncbi.nlm.nih.gov/pubmed/25062915
http://dx.doi.org/10.1093/gbe/evu161
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