A5008029302- Enzyme Structure and Function
- Photosynthetic Processes and Mechanisms
- Bacterial Genetics and Biotechnology
- Circadian rhythm and melatonin
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- Amino Acid Enzymes and Metabolism
- Porphyrin Metabolism and Disorders
- Neurological diseases and metabolism
- Folate and B Vitamins Research
- Light effects on plants
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Cancer-related gene regulation
- Protein Structure and Dynamics
- Photoreceptor and optogenetics research
- Algal biology and biofuel production
- Protist diversity and phylogeny
- Plant and Biological Electrophysiology Studies
- Microbial Metabolism and Applications
- Fungal and yeast genetics research
- Genetic Neurodegenerative Diseases
- Antimicrobial Resistance in Staphylococcus
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
University of California, San Diego
2019-2023
University of Georgia
2014-2019
Circadian (United States)
2019
Joint Center for Structural Genomics
2008-2010
Genomics Institute of the Novartis Research Foundation
2008-2010
Novartis (Switzerland)
2010
A biological clock in a test tube The of cyanobacteria, which remarkably requires just three proteins, has been reconstituted vitro system that allows detailed study its inputs and outputs, bringing new understanding how environmental signals can influence oscillator the controls cellular events such as gene transcription. Chavan et al . extended known function core components to include output transcriptional regulation allow monitoring through fluorescence measurements real time. authors...
Strains of the freshwater cyanobacterium Synechococcus elongatus were first isolated approximately 60 years ago, and PCC 7942 is well established as a model for photosynthesis, circadian biology, biotechnology research. The recent isolation UTEX 3055 subsequent discoveries in biofilm phototaxis phenotypes suggest that lab strains S. are highly domesticated. We performed comprehensive genome comparison among available genomes sequenced two additional laboratory to trace loss native from...
RidA, the archetype member of widely conserved RidA/YER057c/UK114 family proteins, prevents reactive enamine/imine intermediates from accumulating in Salmonella enterica by catalyzing their hydrolysis to stable keto acid products. In absence endogenous 2-aminoacrylate persists cellular environment long enough damage a growing list essential metabolic enzymes. Prior studies have focused on dehydration serine pyridoxal 5'-phosphate (PLP)-dependent serine/threonine dehydratases, IlvA and TdcB,...
The reactive enamine 2-aminoacrylate (2AA) is a metabolic stressor capable of damaging cellular components. Members the broadly conserved Rid (RidA/YER057c/UK114) protein family mitigate 2AA stress in vivo by facilitating and/or imine hydrolysis. Previous work showed that accumulation ridA strains Salmonella enterica led to inactivation multiple target enzymes, including serine hydroxymethyltransferase (GlyA). However, specific cause strain's inability grow during periods had yet be...
Pleckstrin homology (PH) domains have been identified only in eukaryotic proteins to date. We determined crystal structures for three members of an uncharacterized protein family (Pfam PF08000), which provide compelling evidence the existence PH-like bacteria (PHb). The first two contain a single PHb domain that forms dome-shaped, oligomeric ring with C(5) symmetry. third structure has additional helical hairpin attached at C-terminus and similar but much larger C(12) Thus, both molecular...
A variety of metabolic deficiencies and human diseases arise from the disruption mitochondrial enzymes and/or loss DNA. Mounting evidence shows that eukaryotes have conserved prevent accumulation reactive metabolites cause stress inside mitochondrion. 2-Aminoacrylate is a enamine generated by pyridoxal 5'-phosphate-dependent α,β-eliminases as an obligatory intermediate in breakdown serine. In prokaryotes, members broadly RidA family (PF14588) deaminating 2-aminoacrylate to pyruvate. Here, we...
Summary Unchecked amino acid accumulation in living cells has the potential to cause stress by disrupting normal metabolic processes. Thus, many organisms have evolved degradation strategies that prevent endogenous of acids. L‐2,3‐diaminopropionate (Dap) is a non‐protein produced nature where it serves as precursor siderophores, neurotoxins and antibiotics. Dap Salmonella enterica was previously shown inhibit growth unknown mechanisms. The production diaminopropionate ammonia‐lyase (DpaL)...
SsgA-like proteins (SALPs) are a family of homologous cell division-related that occur exclusively in morphologically complex actinomycetes. We show SsgB, subfamily SALPs, is the archetypal SALP functionally conserved all sporulating Sporulation-specific division Streptomyces coelicolor ssgB mutants restored by introduction distant orthologues from other Interestingly, number septa (and spores) complemented null dictated specific orthologue expressed. The crystal structure SsgB Thermobifida...
The protein SO4266 (gi|24375750) from the bacterium Shewanella oneidensis MR-1 is annotated as a member of Pfam PF02661. This family consists Fic (filamentation induced by cAMP) proteins and their relatives, characterized presence well-conserved HPFXXGNG motif.1 biochemistry has not been extensively exact molecular functions remain unknown. From early studies in Escherichia coli, it believed that cAMP may be involved regulatory mechanism cell division, including folate metabolism synthesis...
In Salmonella enterica, 2-aminoacrylate (2AA) is a reactive enamine intermediate generated during number of biochemical reactions. When the 2-iminobutanoate/2-iminopropanoate deaminase (RidA; EC: 3.5.99.10) eliminated, 2AA accumulates and inhibits activity multiple pyridoxal 5'-phosphate(PLP)-dependent enzymes. this study, untargeted proton nuclear magnetic resonance (1H NMR) metabolomics transcriptomics data were used to uncover global metabolic response S. enterica accumulation 2AA. The...
ECX21941 represents a very large family (over 600 members) of novel, ocean metagenome-specific proteins identified by clustering the dataset from Global Ocean Sampling expedition. The crystal structure reveals unexpected similarity to Sm/LSm proteins, which are important RNA-binding despite no detectable sequence similarity. protein assembles as homopentamer in solution and when expressed Escherichia coli first pentameric for this although actual oligomeric form vivo is currently not known....
Coenzyme A (CoA) is a ubiquitous coenzyme involved in fundamental metabolic processes. CoA synthesized from pantothenic acid by pathway that largely conserved among bacteria and eukaryotes consists of five enzymatic steps. While higher organisms, including humans, must scavenge pantothenate the environment, most plants are capable de novo biosynthesis. In Salmonella enterica, precursors to can be salvaged, but subsequent intermediates not transported due their phosphorylated state, thus...
Proteins with the DUF2063 domain constitute a new Pfam family, PF09836. The crystal structure of member this NGO1945 from Neisseria gonorrhoeae, has been determined and reveals that N-terminal is likely to be DNA-binding domain. In conjunction rest protein, involved in transcriptional regulation, which consistent genomic neighborhood analysis. Of 216 currently known proteins contain domain, most significant sequence homologs (∼40–99% identity) are various Haemophilus species. As these...
Microorganisms respond to a variety of metabolic perturbations by repurposing or recruiting pathways reroute flux and overcome the perturbation. Elimination 2-dehydropantoate 2-reductase, PanE, both reduces total coenzyme A (CoA) levels causes conditional HMP-P auxotrophy in Salmonella enterica. CoA acetyl-CoA has no demonstrable effect on synthase, ThiC, vitro. Suppressors aimed at probing connection between biosynthesis thiamine contained mutations gene encoding ilvC transcriptional...
Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this have predominantly been identified in microbes found human gut and oral cavity. The crystal structure one member family, BVU2987 from Bacteroides vulgatus, has determined, revealing β-lactamase inhibitor protein-like with tandem repeat domains. Sequence analysis structural comparisons reveal other proteins are related to protein, PepSY SmpA_OmlA hence likely function as inhibitory proteins.
The RidA subfamily of the Rid (YjgF/YER057c/UK114) superfamily proteins is broadly distributed and found in all domains life. are enamine/imine deaminases. In organisms that have been investigated, lack results accumulation reactive enamine species 2-aminoacrylate (2AA) and/or its derivative imine 2-iminopropanoate (2IP). accumulated can damage specific pyridoxal phosphate (PLP)-dependent target enzymes. metabolic imbalance resulting from damaged enzymes organism based on network...
The crystal structures of SPO0140 and Sbal_2486 were determined using the semiautomated high-throughput pipeline Joint Center for Structural Genomics (JCSG) as part NIGMS Protein Structure Initiative (PSI). revealed a conserved core with domain duplication superficial similarity C-terminal to pleckstrin homology-like folds. conservation interface indicates potential binding site that is likely involve nucleotide-based ligand, genome-context gene-fusion analyses additionally supporting role...
ABSTRACT Reactive enamine stress caused by intracellular 2-aminoacrylate accumulation leads to pleiotropic growth defects in a variety of organisms. Members the well-conserved RidA/YER057c/UK114 protein family prevent enhancing breakdown pyruvate. In Salmonella enterica , disruption RidA allows accumulate and inactivate pyridoxal 5′-phosphate-dependent enzymes generating covalent bonds with enzyme and/or cofactor. This study was initiated identify mechanisms that can overcome absence RidA....
Abstract The histidine kinase SasA enhances robustness of circadian rhythms in the cyanobacterium S. elongatus by temporally controlling expression core clock components, kaiB and kaiC . Here we show that also engages directly with KaiB KaiC proteins to regulate period enhance reconstituted oscillator vitro , particularly under limiting concentrations KaiB. In contrast its role regulating gene expression, function does not require activity; rather, uses structural mimicry cooperatively...
The crystal structures of BB2672 and SPO0826 were determined to resolutions 1.7 2.1 Å by single-wavelength anomalous dispersion multiple-wavelength dispersion, respectively, using the semi-automated high-throughput pipeline Joint Center for Structural Genomics (JCSG) as part NIGMS Protein Structure Initiative (PSI). These proteins are first structural representatives PF06684 (DUF1185) Pfam family. analysis revealed that both adopt a variant Bacillus chorismate mutase fold (BCM). biological...
ABSTRACT The cyanobacterium Synechococcus elongatus PCC 7942 produces an active prokaryotic Argonaute nuclease, SeAgo, whose function is unknown. Here, we show that SeAgo reduces natural transformation and prevents the maintenance of RSF1010 replicons in S. . In addition, a Cas4-like nuclease two other proteins, UvrD RecJ cy (cyanobacterial lineage), were found to reduce transfer or replicons. Like Argonautes, our results indicate provides defense against invading DNA. An ago deletion strain...