The natural history of biocatalytic mechanisms.

Phylogenomic analysis of the occurrence and abundance of protein domains in proteomes has recently showed that the α/β architecture is probably the oldest fold design. This holds important implications for the origins of biochemistry. Here we explore structure-function relationships addressing the u...

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Autores principales:	Neetika Nath, John B O Mitchell, Gustavo Caetano-Anollés
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c269b62b51b74a46a42cd6459169997b
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spelling	oai:doaj.org-article:c269b62b51b74a46a42cd6459169997b2021-11-11T05:52:08ZThe natural history of biocatalytic mechanisms.1553-734X1553-735810.1371/journal.pcbi.1003642https://doaj.org/article/c269b62b51b74a46a42cd6459169997b2014-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24874434/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Phylogenomic analysis of the occurrence and abundance of protein domains in proteomes has recently showed that the α/β architecture is probably the oldest fold design. This holds important implications for the origins of biochemistry. Here we explore structure-function relationships addressing the use of chemical mechanisms by ancestral enzymes. We test the hypothesis that the oldest folds used the most mechanisms. We start by tracing biocatalytic mechanisms operating in metabolic enzymes along a phylogenetic timeline of the first appearance of homologous superfamilies of protein domain structures from CATH. A total of 335 enzyme reactions were retrieved from MACiE and were mapped over fold age. We define a mechanistic step type as one of the 51 mechanistic annotations given in MACiE, and each step of each of the 335 mechanisms was described using one or more of these annotations. We find that the first two folds, the P-loop containing nucleotide triphosphate hydrolase and the NAD(P)-binding Rossmann-like homologous superfamilies, were α/β architectures responsible for introducing 35% (18/51) of the known mechanistic step types. We find that these two oldest structures in the phylogenomic analysis of protein domains introduced many mechanistic step types that were later combinatorially spread in catalytic history. The most common mechanistic step types included fundamental building blocks of enzyme chemistry: "Proton transfer," "Bimolecular nucleophilic addition," "Bimolecular nucleophilic substitution," and "Unimolecular elimination by the conjugate base." They were associated with the most ancestral fold structure typical of P-loop containing nucleotide triphosphate hydrolases. Over half of the mechanistic step types were introduced in the evolutionary timeline before the appearance of structures specific to diversified organisms, during a period of architectural diversification. The other half unfolded gradually after organismal diversification and during a period that spanned ∼2 billion years of evolutionary history.Neetika NathJohn B O MitchellGustavo Caetano-AnollésPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 5, p e1003642 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Neetika Nath John B O Mitchell Gustavo Caetano-Anollés The natural history of biocatalytic mechanisms.
description	Phylogenomic analysis of the occurrence and abundance of protein domains in proteomes has recently showed that the α/β architecture is probably the oldest fold design. This holds important implications for the origins of biochemistry. Here we explore structure-function relationships addressing the use of chemical mechanisms by ancestral enzymes. We test the hypothesis that the oldest folds used the most mechanisms. We start by tracing biocatalytic mechanisms operating in metabolic enzymes along a phylogenetic timeline of the first appearance of homologous superfamilies of protein domain structures from CATH. A total of 335 enzyme reactions were retrieved from MACiE and were mapped over fold age. We define a mechanistic step type as one of the 51 mechanistic annotations given in MACiE, and each step of each of the 335 mechanisms was described using one or more of these annotations. We find that the first two folds, the P-loop containing nucleotide triphosphate hydrolase and the NAD(P)-binding Rossmann-like homologous superfamilies, were α/β architectures responsible for introducing 35% (18/51) of the known mechanistic step types. We find that these two oldest structures in the phylogenomic analysis of protein domains introduced many mechanistic step types that were later combinatorially spread in catalytic history. The most common mechanistic step types included fundamental building blocks of enzyme chemistry: "Proton transfer," "Bimolecular nucleophilic addition," "Bimolecular nucleophilic substitution," and "Unimolecular elimination by the conjugate base." They were associated with the most ancestral fold structure typical of P-loop containing nucleotide triphosphate hydrolases. Over half of the mechanistic step types were introduced in the evolutionary timeline before the appearance of structures specific to diversified organisms, during a period of architectural diversification. The other half unfolded gradually after organismal diversification and during a period that spanned ∼2 billion years of evolutionary history.
format	article
author	Neetika Nath John B O Mitchell Gustavo Caetano-Anollés
author_facet	Neetika Nath John B O Mitchell Gustavo Caetano-Anollés
author_sort	Neetika Nath
title	The natural history of biocatalytic mechanisms.
title_short	The natural history of biocatalytic mechanisms.
title_full	The natural history of biocatalytic mechanisms.
title_fullStr	The natural history of biocatalytic mechanisms.
title_full_unstemmed	The natural history of biocatalytic mechanisms.
title_sort	natural history of biocatalytic mechanisms.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/c269b62b51b74a46a42cd6459169997b
work_keys_str_mv	AT neetikanath thenaturalhistoryofbiocatalyticmechanisms AT johnbomitchell thenaturalhistoryofbiocatalyticmechanisms AT gustavocaetanoanolles thenaturalhistoryofbiocatalyticmechanisms AT neetikanath naturalhistoryofbiocatalyticmechanisms AT johnbomitchell naturalhistoryofbiocatalyticmechanisms AT gustavocaetanoanolles naturalhistoryofbiocatalyticmechanisms
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The natural history of biocatalytic mechanisms.

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