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...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	PLoS computational biology Ročník 10; číslo 5; s. e1003642
Hlavní autoři:	Nath, Neetika, Mitchell, John B. O., Caetano-Anollés, Gustavo
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 01.05.2014 Public Library of Science (PLoS)
Témata:	Architecture Biochemistry Biology and Life Sciences Catalysis Chemical reactions Classification Enzymes Enzymes - chemistry Enzymes - genetics Enzymes - ultrastructure Evolution Evolution, Molecular Metabolism Metabolites Phylogeny Physical Sciences Physiological aspects Protein Folding Protein research Protein Structure, Tertiary Proteins Structure-Activity Relationship
ISSN:	1553-7358, 1553-734X, 1553-7358
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: NN JBOM GCA. Performed the experiments: NN. Analyzed the data: NN JBOM GCA. Contributed reagents/materials/analysis tools: NN JBOM GCA. Wrote the paper: NN JBOM GCA. The authors have declared that no competing interests exist.
ISSN:	1553-7358 1553-734X 1553-7358
DOI:	10.1371/journal.pcbi.1003642