Evidence for the Existence of Elaborate Enzyme Complexes in the Paleoarchean Era (original) (raw)
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Biochemistry, 2005
myo-Inositol-1-phosphate synthase (mIPS) catalyzes the first step in the synthesis of L-myoinositol-1-phosphate. We have solved and refined the structure of the mIPS from the hyperthermophilic sulfate reducer Archaeoglobus fulgidus at 1.9 Å resolution. The enzyme crystallized from poly(ethylene glycol) in the P1 space group with one tetramer in the asymmetric unit and provided a view of the entire biologically active oligomer. Despite significant changes in sequence length and amino acid composition, the general architecture of the archaeal enzyme is similar to that of the eukaryotic mIPS from Saccharomyces cereVisiae and bacterial mIPS from Mycobacterium tuberculosis. The enhanced thermostability of the archaeal enzyme as compared to that from yeast is consistent with deletion of a number of surface loops that results in a significantly smaller protein. In the structure of the A. fulgidus mIPS, the active sites of all four subunits were fully ordered and contained NAD + and inorganic phosphate. The structure also contained a single metal ion (identified as K +) in two of the four subunits. The analysis of the electrostatic potential maps of the protein suggested the presence of a second metal-ion-binding site in close proximity to the first metal ion and NAD +. The modeling of the substrate and known inhibitors suggests a critical role for the second metal ion in catalysis and provides insights into the common elements of the catalytic cycle in enzymes from different life kingdoms.
Single-molecule paleoenzymology probes the chemistry of resurrected enzymes
Nature Structural & Molecular Biology, 2011
It is possible to travel back in time at the molecular level by reconstructing proteins from extinct organisms. Here we report the reconstruction, based on sequence predicted by phylogenetic analysis, of seven Precambrian thioredoxin enzymes (Trx) dating back between ~1.4 and ~4 billion years (Gyr). The reconstructed enzymes are up to 32 °C more stable than modern enzymes, and the
Origin of Proteins in a Prebiotic World, 2024
Understanding the origin of enzymatic proteins and catalysts on prebiotic Earth remains a complex and unresolved challenge. These molecules are essential for life, accelerating chemical reactions necessary for biological functions. However, their origins are paradoxical, as the synthesis of complex proteins typically requires catalysts, which are themselves proteins. This paper explores the multifaceted challenges associated with this paradox, including energy sources for synthesis, early catalysis, and peptide formation, peptide bond formation, mineral surface interactions, the transition from abiotic catalysts, and early structural and functional stability. By investigating these areas, we aim to shed light on the critical steps that led to the sophisticated enzymatic systems vital for life today.
Widespread Recruitment of Ancient Domain Structures in Modern Enzymes during Metabolic Evolution
2013
Protein domains sometime combine to form multidomain proteins and are acquired or lost in lineages of organisms. These processes are ubiquitous in modern metabolism. To sort out evolutionary patterns of domain recruitment, we developed an algorithm that derives the most plausible ancestry of an enzyme from structural and evolutionary annotations in the MANET database. We applied this algorithm to the analysis of 1,163 enzymes with structural assignments. We then counted the number of enzymes along a time series and analyzed enzyme distribution in organisms belonging to superkingdoms Archaea, Bacteria, and Eukarya. The generated timelines described the evolution of modern metabolic networks and showed an early build-up of metabolic activities associated with metabolism of nucleotides, cofactors, and vitamins, followed by enzymes involved in carbohydrate and amino acid metabolism. More importantly, we find that existing domain structures were pervasively co-opted to perform more modern enzymatic tasks, either singly or in combination with other domains. This occurred differentially in lineages of the superkingdoms as the world diversified and organisms adapted to various environments. Our results highlight the important role of recruitment and domain organization in metabolic evolution.
The Classification and Evolution of Enzyme Function
Biophysical Journal, 2015
Enzymes are the proteins responsible for the catalysis of life. Enzymes sharing a common ancestor as defined by sequence and structure similarity are grouped into families and superfamilies. The molecular function of enzymes is defined as their ability to catalyze biochemical reactions; it is manually classified by the Enzyme Commission and robust approaches to quantitatively compare catalytic reactions are just beginning to appear. Here, we present an overview of studies at the interface of the evolution and function of enzymes.
The Natural History of Biocatalytic Mechanisms
PLoS Computational Biology, 2014
Phylogenomic analysis of the occurrence and abundance of protein domains in proteomes has recently showed that the a/ b 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 a/b 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 Ploop 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.
Characters of very ancient proteins
Biochemical and …, 2008
Tracing the characters of very ancient proteins represents one of the biggest challenges in the study of origin of life. Although there are no primitive protein fossils remaining, the characters of very ancient proteins can be traced by molecular fossils embedded in modern proteins. In this paper, first the prior findings in this area are outlined and then a new strategy is proposed to address the intriguing issue. It is interesting to find that various molecular fossils and different protein datasets lead to similar conclusions on the features of very ancient proteins, which can be summarized as follows: (i) the architectures of very ancient proteins belong to the following folds: P-loop containing nucleoside triphosphate hydrolases (c.37), TIM beta/alpha-barrel (c.1), NAD(P)-binding Rossmann-fold domains (c.2), Ferredoxin-like (d.58), Flavodoxin-like (c.23) and Ribonuclease H-like motif (c.55); (ii) the functions of very ancient proteins are related to the metabolisms of purine, pyrimidine, porphyrin, chlorophyll and carbohydrates; (iii) a certain part of very ancient proteins need cofactors (such as ATP, NADH or NADPH) to work normally.
The Origin of Modern Metabolic Networks Inferred from Phylogenomic Analysis of Protein Architecture
Proceedings of The National Academy of Sciences, 2007
Metabolism represents a complex collection of enzymatic reactions and transport processes that convert metabolites into molecules capable of supporting cellular life. Here we explore the origins and evolution of modern metabolism. Using phylogenomic information linked to the structure of metabolic enzymes, we sort out recruitment processes and discover that most enzymatic activities were associated with the nine most ancient and widely distributed protein fold architectures. An analysis of newly discovered functions showed enzymatic diversification occurred early, during the onset of the modern protein world. Most importantly, phylogenetic reconstruction exercises and other evidence suggest strongly that metabolism originated in enzymes with the P-loop hydrolase fold in nucleotide metabolism, probably in pathways linked to the purine metabolic subnetwork. Consequently, the first enzymatic takeover of an ancient biochemistry or prebiotic chemistry was related to the synthesis of nucleotides for the RNA world. enzyme activity ͉ evolution ͉ metabolism ͉ nucleotide metabolism T here is current interest in the processes underlying the biology of network because these offer insight into the organization and evolution of life (1). Cellular metabolism, one of the greatest achievements of science, is clearly the best-studied biological network. It represents a complex collection of enzymatic reactions and transport processes that convert metabolites into molecules capable of supporting cells and organisms. However, our knowledge of how modern metabolism originated and evolved is limited (2). One widely accepted hypothesis is that promiscuous catalytic activities in proteins provide a selective advantage and are recruited to perform new metabolic functions (3, 4). Considerable evidence supports a patchwork recruitment scenario in which recruited homologous enzymes are scattered over diverse pathways (2). For example, enzymes with ␣/ barrel fold structure that catalyze similar reactions occur across metabolic subnetworks (5, 6) and a small set of structural families dominates the small-molecule metabolism in Escherichia coli (7-10). The recruitment hypothesis assumes there is already an active enzymatic core with multifunctional enzymes from which proteins are drawn for metabolic innovation. Because history restricts the interplay between structure and function of metabolic enzymes, we here use evolutionary patterns in protein structure advantageously to study recruitment processes and metabolic network evolution.