Role of Proline Residues in the Folding of Serine Hydroxymethyltransferase

Fu, Tzu Fun; Boja, Emily S.; Schirch, Verne

doi:10.1074/jbc.m303779200

Cited by 26 publications

(23 citation statements)

References 19 publications

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“…To determine of K D for 5f-THF in the presence of added DHFR/ADK, the concentration of the latter was fixed at 60 µM. The procedure followed is essentially described in (Fu et al, 2003). …”

Section: Methodsmentioning

confidence: 99%

Transient protein-protein interactions perturb E. coli metabolome and cause gene dosage toxicity

Bhattacharyya

Bershtein

Yan

et al. 2016

eLife

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Gene dosage toxicity (GDT) is an important factor that determines optimal levels of protein abundances, yet its molecular underpinnings remain unknown. Here, we demonstrate that overexpression of DHFR in E. coli causes a toxic metabolic imbalance triggered by interactions with several functionally related enzymes. Though deleterious in the overexpression regime, surprisingly, these interactions are beneficial at physiological concentrations, implying their functional significance in vivo. Moreover, we found that overexpression of orthologous DHFR proteins had minimal effect on all levels of cellular organization – molecular, systems, and phenotypic, in sharp contrast to E. coli DHFR. Dramatic difference of GDT between ‘E. coli’s self’ and ‘foreign’ proteins suggests the crucial role of evolutionary selection in shaping protein-protein interaction (PPI) networks at the whole proteome level. This study shows how protein overexpression perturbs a dynamic metabolon of weak yet potentially functional PPI, with consequences for the metabolic state of cells and their fitness.DOI: http://dx.doi.org/10.7554/eLife.20309.001

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Section: Methodsmentioning

confidence: 99%

Transient protein-protein interactions perturb E. coli metabolome and cause gene dosage toxicity

Bhattacharyya

Bershtein

Yan

et al. 2016

eLife

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“…In the second, slower phase, the enzyme folds into the native structure, acquiring the capability to bind the cofactor. Although the crystallographic data have provided a framework for a better understanding of folding studies [35], the key events required for the transition from the first to the second phase remain unclear. Most work on SHMT has focused on enzymes from mesophilic bacteria and eukaryotic organisms.…”

Section: Shmtmentioning

confidence: 99%

Extremophilic SHMTs: From Structure to Biotechnology

Angelaccio

2013

BioMed Research International

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Recent advances in molecular and structural biology have improved the availability of virtually any biocatalyst in large quantity and have also provided an insight into the detailed structure-function relationships of many of them. These results allowed the rational exploitation of biocatalysts for use in organic synthesis. In this context, extremophilic enzymes are extensively studied for their potential interest for many biotechnological and industrial applications, as they offer increased rates of reactions, higher substrate solubility, and/or longer enzyme half-lives at the conditions of industrial processes. Serine hydroxymethyltransferase (SHMT), for its ubiquitous nature, represents a suitable model for analyzing enzyme adaptation to extreme environments. In fact, many SHMT sequences from Eukarya, Eubacteria and Archaea are available in data banks as well as several crystal structures. In addition, SHMT is structurally conserved because of its critical metabolic role; consequently, very few structural changes have occurred during evolution. Our research group analyzed the molecular basis of SHMT adaptation to high and low temperatures, using experimental and comparative in silico approaches. These structural and functional studies of SHMTs purified from extremophilic organisms can help to understand the peculiarities of the enzyme activity at extreme temperatures, indicating possible strategies for rational enzyme engineering.

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“…SHMT catalyzes the reversible interconversion of serine and glycine by transferring the hydroxymethyl group of L-Ser to 5,6,7,8-tetrahydrofolate to yield Gly and 5,10-methylenetetrahydorfolate (Fu, Boja, Safo et al 2003). This reaction is the major source of single-carbon groups required for the synthesis of purine, thymidylate, and methionine.…”

Section: Signature Sequences Uniquely Shared By the Bacteroidetes Chmentioning

confidence: 99%

The Phylogeny and Signature Sequences Characteristics ofFibrobacteres,Chlorobi, andBacteroidetes

Gupta

2004

Critical Reviews in Microbiology

105

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Fibrobacteres, Chlorobi, and Bacteroidetes (FCB group) comprise three main bacterial phyla recognized on the basis of 16S rRNA trees. Presently, there are no distinctive biochemical or molecular characteristics known that can distinguish these bacteria from other bacterial phyla. The relationship of these bacteria to other phyla is also not known. This review describes many signatures, consisting of defined and conserved inserts in widely distributed proteins, that provide distinctive molecular markers for these groups of bacteria. These signatures serve to clarify the evolutionary relationship between members of the FCB group, and to other bacterial phyla. A 4 aa insert in DNA Gyrase B (GyrB) and a 45 aa insert in the SecA proteins are uniquely shared by various Bacteroidetes species. The insert in GyrB is present in all Bacteroidetes species (>100) covering different orders and families, indicating that it is a distinctive characteristic of the group. Three signatures consisting of an 18 aa insert in ATPase alpha-subunit, an 8-9 aa insert in the FtsK protein and a 1 aa insert in the UvrB protein are commonly shared only by the Bacteroidetes and Chlorobi homologs providing evidence that these two groups are specifically related to each other. Two additional inserts in the RNA polymerase beta'-subunit (5-7 aa) and Serine hydroxymethyl-transferase (14-16 aa), which are commonly present in various Bacteroidetes, Chlorobi, and Fibrobacteres homologs, but not any other bacteria, provide evidence that these groups shared a common ancestor exclusive of all other bacteria. The FCB groups of bacteria are indicated to have diverged from this common ancestor in the following order: Fibrobacteres --> Chlorobi --> Bacteriodetes. The inferences from signature sequences are strongly supported by phylogenetic analyses. These observations suggest that the FCB groups of bacteria should be placed in a single phylum rather than three distinct phyla. Signature sequences in a number of other proteins provide evidence that the FCB group of bacteria diverged at a similar time as the Chlamydiae group, and that the Spirochetes and Aquificales groups are its closest relatives.

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Role of Proline Residues in the Folding of Serine Hydroxymethyltransferase

Cited by 26 publications

References 19 publications

Transient protein-protein interactions perturb E. coli metabolome and cause gene dosage toxicity

Transient protein-protein interactions perturb E. coli metabolome and cause gene dosage toxicity

Extremophilic SHMTs: From Structure to Biotechnology

The Phylogeny and Signature Sequences Characteristics ofFibrobacteres,Chlorobi, andBacteroidetes

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