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Experimental and computational analysis of the ancestry of an evolutionary young enzyme from histidine biosynthesis
The conservation of fold and chemistry of the enzymes associated with histidine biosynthesis suggests that this pathway evolved prior to the diversification of Bacteria, Archaea, and Eukaryotes. The only exception is the histidinol phosphate phosphatase (HolPase). So far, non‐homologous HolPases tha...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9798254/ https://www.ncbi.nlm.nih.gov/pubmed/36502290 http://dx.doi.org/10.1002/pro.4536 |
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author | Kinateder, Thomas Drexler, Lukas Straub, Kristina Merkl, Rainer Sterner, Reinhard |
author_facet | Kinateder, Thomas Drexler, Lukas Straub, Kristina Merkl, Rainer Sterner, Reinhard |
author_sort | Kinateder, Thomas |
collection | PubMed |
description | The conservation of fold and chemistry of the enzymes associated with histidine biosynthesis suggests that this pathway evolved prior to the diversification of Bacteria, Archaea, and Eukaryotes. The only exception is the histidinol phosphate phosphatase (HolPase). So far, non‐homologous HolPases that possess distinct folds and belong to three different protein superfamilies have been identified in various phylogenetic clades. However, their evolution has remained unknown to date. Here, we analyzed the evolutionary history of the HolPase from γ‐Proteobacteria (HisB‐N). It has been argued that HisB‐N and its closest homologue d‐glycero‐d‐manno‐heptose‐1,7‐bisphosphate 7‐phosphatase (GmhB) have emerged from the same promiscuous ancestral phosphatase. GmhB variants catalyze the hydrolysis of the anomeric d‐glycero‐d‐manno‐heptose‐1,7‐bisphosphate (αHBP or βHBP) with a strong preference for one anomer (αGmhB or βGmhB). We found that HisB‐N from Escherichia coli shows promiscuous activity for βHBP but not αHBP, while βGmhB from Crassaminicella sp. shows promiscuous activity for HolP. Accordingly, a combined phylogenetic tree of αGmhBs, βGmhBs, and HisB‐N sequences revealed that HisB‐Ns form a compact subcluster derived from βGmhBs. Ancestral sequence reconstruction and in vitro analysis revealed a promiscuous HolPase activity in the resurrected enzymes prior to functional divergence of the successors. The following increase in catalytic efficiency of the HolP turnover is reflected in the shape and electrostatics of the active site predicted by AlphaFold. An analysis of the phylogenetic tree led to a revised evolutionary model that proposes the horizontal gene transfer of a promiscuous βGmhB from δ‐ to γ‐Proteobacteria where it evolved to the modern HisB‐N. |
format | Online Article Text |
id | pubmed-9798254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97982542023-01-05 Experimental and computational analysis of the ancestry of an evolutionary young enzyme from histidine biosynthesis Kinateder, Thomas Drexler, Lukas Straub, Kristina Merkl, Rainer Sterner, Reinhard Protein Sci Full‐length Papers The conservation of fold and chemistry of the enzymes associated with histidine biosynthesis suggests that this pathway evolved prior to the diversification of Bacteria, Archaea, and Eukaryotes. The only exception is the histidinol phosphate phosphatase (HolPase). So far, non‐homologous HolPases that possess distinct folds and belong to three different protein superfamilies have been identified in various phylogenetic clades. However, their evolution has remained unknown to date. Here, we analyzed the evolutionary history of the HolPase from γ‐Proteobacteria (HisB‐N). It has been argued that HisB‐N and its closest homologue d‐glycero‐d‐manno‐heptose‐1,7‐bisphosphate 7‐phosphatase (GmhB) have emerged from the same promiscuous ancestral phosphatase. GmhB variants catalyze the hydrolysis of the anomeric d‐glycero‐d‐manno‐heptose‐1,7‐bisphosphate (αHBP or βHBP) with a strong preference for one anomer (αGmhB or βGmhB). We found that HisB‐N from Escherichia coli shows promiscuous activity for βHBP but not αHBP, while βGmhB from Crassaminicella sp. shows promiscuous activity for HolP. Accordingly, a combined phylogenetic tree of αGmhBs, βGmhBs, and HisB‐N sequences revealed that HisB‐Ns form a compact subcluster derived from βGmhBs. Ancestral sequence reconstruction and in vitro analysis revealed a promiscuous HolPase activity in the resurrected enzymes prior to functional divergence of the successors. The following increase in catalytic efficiency of the HolP turnover is reflected in the shape and electrostatics of the active site predicted by AlphaFold. An analysis of the phylogenetic tree led to a revised evolutionary model that proposes the horizontal gene transfer of a promiscuous βGmhB from δ‐ to γ‐Proteobacteria where it evolved to the modern HisB‐N. John Wiley & Sons, Inc. 2023-01-01 /pmc/articles/PMC9798254/ /pubmed/36502290 http://dx.doi.org/10.1002/pro.4536 Text en © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Full‐length Papers Kinateder, Thomas Drexler, Lukas Straub, Kristina Merkl, Rainer Sterner, Reinhard Experimental and computational analysis of the ancestry of an evolutionary young enzyme from histidine biosynthesis |
title | Experimental and computational analysis of the ancestry of an evolutionary young enzyme from histidine biosynthesis |
title_full | Experimental and computational analysis of the ancestry of an evolutionary young enzyme from histidine biosynthesis |
title_fullStr | Experimental and computational analysis of the ancestry of an evolutionary young enzyme from histidine biosynthesis |
title_full_unstemmed | Experimental and computational analysis of the ancestry of an evolutionary young enzyme from histidine biosynthesis |
title_short | Experimental and computational analysis of the ancestry of an evolutionary young enzyme from histidine biosynthesis |
title_sort | experimental and computational analysis of the ancestry of an evolutionary young enzyme from histidine biosynthesis |
topic | Full‐length Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9798254/ https://www.ncbi.nlm.nih.gov/pubmed/36502290 http://dx.doi.org/10.1002/pro.4536 |
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