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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 -
Proceedings of the National Academy of... Jan 2022
Topics: Bacteria; Biological Evolution; Multienzyme Complexes
PubMed: 34996854
DOI: 10.1073/pnas.2120286118 -
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 -
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 -
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 -
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 -
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 -
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 -
Biochimica Et Biophysica Acta Jan 2002The epsilon-proteobacteria form a subdivision of the Proteobacteria including the genera Wolinella, Campylobacter, Helicobacter, Sulfurospirillum, Arcobacter and... (Comparative Study)
Comparative Study Review
The epsilon-proteobacteria form a subdivision of the Proteobacteria including the genera Wolinella, Campylobacter, Helicobacter, Sulfurospirillum, Arcobacter and Dehalospirillum. The majority of these bacteria are oxidase-positive microaerophiles indicating an electron transport chain with molecular oxygen as terminal electron acceptor. However, numerous members of the epsilon-proteobacteria also grow in the absence of oxygen. The common presence of menaquinone and fumarate reduction activity suggests anaerobic fumarate respiration which was demonstrated for the rumen bacterium Wolinella succinogenes as well as for Sulfurospirillum deleyianum, Campylobacter fetus, Campylobacter rectus and Dehalospirillum multivorans. To date, complete genome sequences of Helicobacter pylori and Campylobacter jejuni are available. These bacteria and W. succinogenes contain the genes frdC, A and B encoding highly similar heterotrimeric enzyme complexes belonging to the family of succinate:quinone oxidoreductases. The crystal structure of the W. succinogenes quinol:fumarate reductase complex (FrdCAB) was solved recently, thus providing a model of succinate:quinone oxidoreductases from epsilon-proteobacteria. Succinate:quinone oxidoreductases are being discussed as possible therapeutic targets in the treatment of several pathogenic epsilon-proteobacteria.
Topics: Citric Acid Cycle; Electron Transport; Electron Transport Complex II; Energy Metabolism; Fumarates; Models, Chemical; Models, Molecular; Multienzyme Complexes; Operon; Oxidation-Reduction; Oxidoreductases; Proteobacteria; Succinate Dehydrogenase; Succinic Acid; Wolinella
PubMed: 11803019
DOI: 10.1016/s0005-2728(01)00230-4 -
Metabolic Engineering May 2012Cell-free synthetic biology is emerging as a powerful approach aimed to understand, harness, and expand the capabilities of natural biological systems without using... (Review)
Review
Cell-free synthetic biology is emerging as a powerful approach aimed to understand, harness, and expand the capabilities of natural biological systems without using intact cells. Cell-free systems bypass cell walls and remove genetic regulation to enable direct access to the inner workings of the cell. The unprecedented level of control and freedom of design, relative to in vivo systems, has inspired the rapid development of engineering foundations for cell-free systems in recent years. These efforts have led to programmed circuits, spatially organized pathways, co-activated catalytic ensembles, rational optimization of synthetic multi-enzyme pathways, and linear scalability from the micro-liter to the 100-liter scale. It is now clear that cell-free systems offer a versatile test-bed for understanding why nature's designs work the way they do and also for enabling biosynthetic routes to novel chemicals, sustainable fuels, and new classes of tunable materials. While challenges remain, the emergence of cell-free systems is poised to open the way to novel products that until now have been impractical, if not impossible, to produce by other means.
Topics: Cell-Free System; Multienzyme Complexes; Synthetic Biology
PubMed: 21946161
DOI: 10.1016/j.ymben.2011.09.002