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Proceedings of the National Academy of... Jan 2022
Topics: Bacteria; Biological Evolution; Multienzyme Complexes
PubMed: 34996854
DOI: 10.1073/pnas.2120286118 -
Protein Science : a Publication of the... Apr 2017The SET1 family of proteins, and in particular MLL1, are essential regulators of transcription and key mediators of normal development and disease. Here, we summarize... (Review)
Review
The SET1 family of proteins, and in particular MLL1, are essential regulators of transcription and key mediators of normal development and disease. Here, we summarize the detailed characterization of the methyltransferase activity of SET1 complexes and the role of the key subunits, WDR5, RbBP5, ASH2L, and DPY30. We present new data on full kinetic characterization of human MLL1, MLL3, SET1A, and SET1B trimeric, tetrameric, and pentameric complexes to elaborate on substrate specificities and compare our findings with what has been reported before. We also review exciting recent work identifying potent inhibitors of oncogenic MLL1 function through disruption of protein-protein interactions within the MLL1 complex.
Topics: Enzyme Inhibitors; Histone-Lysine N-Methyltransferase; Humans; Multienzyme Complexes; Myeloid-Lymphoid Leukemia Protein
PubMed: 28160335
DOI: 10.1002/pro.3129 -
Biochemistry Jun 2018Enzymes in biosynthetic pathways, especially in plant and microbial metabolism, generate structural and functional group complexity in small molecules by conversion of... (Review)
Review
Enzymes in biosynthetic pathways, especially in plant and microbial metabolism, generate structural and functional group complexity in small molecules by conversion of acyclic frameworks to cyclic scaffolds via short, efficient routes. The distinct chemical logic used by several distinct classes of cyclases, oxidative and non-oxidative, has recently been elucidated by genome mining, heterologous expression, and genetic and mechanistic analyses. These include enzymes performing pericyclic transformations, pyran synthases, tandem acting epoxygenases, and epoxide "hydrolases", as well as oxygenases and radical S-adenosylmethionine enzymes that involve rearrangements of substrate radicals under aerobic or anaerobic conditions.
Topics: Animals; Biochemical Phenomena; Biosynthetic Pathways; Cyclization; Enzymes; Humans; Metabolic Networks and Pathways; Multienzyme Complexes; Oxygenases
PubMed: 29236467
DOI: 10.1021/acs.biochem.7b01161 -
Biochemistry Jun 2017The organization of metabolic multienzyme complexes has been hypothesized to benefit metabolic processes and provide a coordinated way for the cell to regulate... (Review)
Review
The organization of metabolic multienzyme complexes has been hypothesized to benefit metabolic processes and provide a coordinated way for the cell to regulate metabolism. Historically, their existence has been supported by various in vitro techniques. However, it is only recently that the existence of metabolic complexes inside living cells has come to light to corroborate this long-standing hypothesis. Indeed, subcellular compartmentalization of metabolic enzymes appears to be widespread and highly regulated. On the other hand, it is still challenging to demonstrate the functional significance of these enzyme complexes in the context of the cellular milieu. In this review, we discuss the current understanding of metabolic enzyme complexes by primarily focusing on central carbon metabolism and closely associated metabolic pathways in a variety of organisms, as well as their regulation and functional contributions to cells.
Topics: Animals; Cell Physiological Phenomena; Humans; Metabolic Engineering; Models, Biological; Multienzyme Complexes
PubMed: 28580779
DOI: 10.1021/acs.biochem.7b00249 -
Journal of Biochemistry Feb 1998The proteasome is a multisubunit protease complex with an apparent sedimentation coefficient of 20S. Two types of regulatory complexes, named PA700 and PA28, bind to... (Review)
Review
The proteasome is a multisubunit protease complex with an apparent sedimentation coefficient of 20S. Two types of regulatory complexes, named PA700 and PA28, bind to both ends of the cylindrical 20S proteasome to form the dumbbell-like and football-like proteasomes, respectively. The former complex, named the 26S proteasome, is a eukaryotic ATP-dependent protease and appears to be well organized as a large complex of 2 MDa, consisting of approximately 40 polypeptides, to facilitate rapid proteolysis. It is assumed to be a protein "death machine", destroying a variety of cellular proteins that have acquired a specific degradation signal(s) such as a multiubiquitin chain. Recently data on in vivo substrates for the ubiquitin-proteasome pathway have been accumulating rapidly, implying its involvement in many biologically important processes, such as cell-cycle regulation, signal transduction, protein quality control, and the immune response. The newly-identified PA28 family proteins are inducible by interferons, and may cooperate with the 26S proteasome or play additional roles. Since the proteasome is capable of catalyzing breakdown of proteins not only irreversibly, but also rapidly and timely, it is thought to be a new regulatory system for biological reactions in eukaryotes.
Topics: Animals; Cysteine Endopeptidases; Humans; Multienzyme Complexes; Proteasome Endopeptidase Complex; Structure-Activity Relationship
PubMed: 9538192
DOI: 10.1093/oxfordjournals.jbchem.a021922 -
Virus Research Dec 2014The international response to SARS-CoV has produced an outstanding number of protein structures in a very short time. This review summarizes the findings of functional... (Review)
Review
The international response to SARS-CoV has produced an outstanding number of protein structures in a very short time. This review summarizes the findings of functional and structural studies including those derived from cryoelectron microscopy, small angle X-ray scattering, NMR spectroscopy, and X-ray crystallography, and incorporates bioinformatics predictions where no structural data is available. Structures that shed light on the function and biological roles of the proteins in viral replication and pathogenesis are highlighted. The high percentage of novel protein folds identified among SARS-CoV proteins is discussed.
Topics: Coronavirus; Cryoelectron Microscopy; Crystallography, X-Ray; Magnetic Resonance Spectroscopy; Multienzyme Complexes; RNA-Dependent RNA Polymerase; Scattering, Small Angle
PubMed: 24355834
DOI: 10.1016/j.virusres.2013.12.004 -
Current Biology : CB
Review
Topics: Animals; Catalysis; Cysteine Endopeptidases; Humans; Multienzyme Complexes; Proteasome Endopeptidase Complex; Proteins; Ubiquitins
PubMed: 9889109
DOI: 10.1016/s0960-9822(98)00004-9 -
Journal of Biomedicine & Biotechnology 2011Epigenetic gene silencing is one of the fundamental mechanisms for ensuring proper gene expression patterns during cellular differentiation and development. Histone... (Review)
Review
Epigenetic gene silencing is one of the fundamental mechanisms for ensuring proper gene expression patterns during cellular differentiation and development. Histone deacetylases (HDACs) are evolutionally conserved enzymes that remove acetyl modifications from histones and play a central role in epigenetic gene silencing. In cells, HDAC forms a multiprotein complex (HDAC complex) in which the associated proteins are believed to help HDAC carry out its cellular functions. Though each HDAC complex contains distinct components, the presence of isoforms for some of the components expands the variety of complexes and the diversity of their cellular roles. Recent studies have also revealed a functional link between HDAC complexes and specific histone demethylases. In this paper, we summarize the distinct and cooperative roles of four class I HDAC complexes, Sin3, NuRD, CoREST, and NCoR/SMRT, with respect to their component diversity and their relationship with specific histone demethylases.
Topics: Animals; Epigenesis, Genetic; Histone Deacetylases; Humans; Multienzyme Complexes
PubMed: 21049000
DOI: 10.1155/2011/129383 -
Journal of Molecular Biology Sep 2019Prokaryotic transcription is one of the most studied biological systems, with relevance to many fields including the development and use of antibiotics, the construction... (Review)
Review
Prokaryotic transcription is one of the most studied biological systems, with relevance to many fields including the development and use of antibiotics, the construction of synthetic gene networks, and the development of many cutting-edge methodologies. Here, we discuss recent structural, biochemical, and single-molecule biophysical studies targeting the mechanisms of transcription initiation in bacteria, including the formation of the open complex, the reaction of initial transcription, and the promoter escape step that leads to elongation. We specifically focus on the mechanisms employed by the RNA polymerase holoenzyme with the housekeeping sigma factor σ. The recent progress provides answers to long-held questions, identifies intriguing new behaviours, and opens up fresh questions for the field of transcription.
Topics: Bacteria; DNA, Bacterial; DNA-Directed RNA Polymerases; Multienzyme Complexes; Promoter Regions, Genetic; Sigma Factor; Transcription Initiation, Genetic
PubMed: 31082441
DOI: 10.1016/j.jmb.2019.04.046 -
FEMS Microbiology Reviews Jul 2008The accurate synthesis of proteins, dictated by the corresponding nucleotide sequence encoded in mRNA, is essential for cell growth and survival. Central to this process... (Review)
Review
The accurate synthesis of proteins, dictated by the corresponding nucleotide sequence encoded in mRNA, is essential for cell growth and survival. Central to this process are the aminoacyl-tRNA synthetases (aaRSs), which provide amino acid substrates for the growing polypeptide chain in the form of aminoacyl-tRNAs. The aaRSs are essential for coupling the correct amino acid and tRNA molecules, but are also known to associate in higher order complexes with proteins involved in processes beyond translation. Multiprotein complexes containing aaRSs are found in all three domains of life playing roles in splicing, apoptosis, viral assembly, and regulation of transcription and translation. An overview of the complexes aaRSs form in all domains of life is presented, demonstrating the extensive network of connections between the translational machinery and cellular components involved in a myriad of essential processes beyond protein synthesis.
Topics: Amino Acyl-tRNA Synthetases; Archaea; Bacteria; Eukaryotic Cells; Multienzyme Complexes; Protein Biosynthesis
PubMed: 18522650
DOI: 10.1111/j.1574-6976.2008.00119.x