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Bromodomain
A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducing the signal carried by acetylated lysine residues and translating it into various normal or abnormal phenotypes. Their affinity is higher for regions where multiple acetylation sites exist in proximity. This recognition is often a prerequisite for protein-histone association and chromatin remodeling. The domain itself adopts an all-α protein fold, a bundle of four alpha helices each separated by loop regions of variable lengths that form a hydrophobic pocket that recognizes the acetyl lysine. Discovery The bromodomain was identified as a novel structural motif by John W. Tamkun and colleagues studying the drosophila gene ''Brahma''/''brm'', and showed sequence similarity to genes involved in transcriptional activation. The name "bromo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BET Inhibitor
BET inhibitors are a class of drugs that reversibly bind the bromodomains of Bromodomain and Extra-Terminal motif (BET) proteins BRD2, BRD3, BRD4, and BRDT, and prevent protein-protein interaction between BET proteins and acetylated histones and transcription factors. Discovery and development Thienodiazepine BET inhibitors were discovered by scientists at Yoshitomi Pharmaceuticals (now Mitsubishi Tanabe Pharma) in the early 1990s, and their potential both as anti-inflammatories and anti-cancer agents noted. However, these molecules remained largely unknown until 2010 when both the use of JQ1 in NUT midline carcinoma and of I-BET 762 in sepsis were published. Since this time a number of molecules have been described that are capable of targeting BET bromodomains. BET inhibitors have been described that are able to discriminate between the first and second bromodomains of BET proteins (BD1 vs BD2). However, no BET inhibitor has yet been described that can reliably distinguish ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BET Inhibitors
BET inhibitors are a class of drugs that reversibly bind the bromodomains of Bromodomain and Extra-Terminal motif (BET) proteins BRD2, BRD3, BRD4, and BRDT, and prevent protein-protein interaction between BET proteins and acetylated histones and transcription factors. Discovery and development Thienodiazepine BET inhibitors were discovered by scientists at Yoshitomi Pharmaceuticals (now Mitsubishi Tanabe Pharma) in the early 1990s, and their potential both as anti-inflammatories and anti-cancer agents noted. However, these molecules remained largely unknown until 2010 when both the use of JQ1 in NUT midline carcinoma and of I-BET 762 in sepsis were published. Since this time a number of molecules have been described that are capable of targeting BET bromodomains. BET inhibitors have been described that are able to discriminate between the first and second bromodomains of BET proteins (BD1 vs BD2). However, no BET inhibitor has yet been described that can reliably distinguish ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRD4
Bromodomain-containing protein 4 is a protein that in humans is encoded by the ''BRD4'' gene. BRD4 is a member of the BET (bromodomain and extra terminal domain) family, which also includes BRD2, BRD3, and BRDT. BRD4, similar to other BET family members, contains two bromodomains that recognize acetylated lysine residues. BRD4 also has an extended C-terminal domain with little sequence homology to other BET family members. Structure The two bromodomains in BRD4, termed BD1 and BD2, consist of 4 alpha-helices linked by 2 loops. The ET domain structure is made up of 3 alpha-helices and a loop. The C-terminal domain of BRD4 has been implicated in promoting gene transcription through interaction with the transcription elongation factor P-TEFb and RNA polymerase II. Function The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human BRD2 (RING3) protein, a serine/threonine kinase. Each of the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Histone Acetyltransferases
Histone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-''N''-acetyllysine. DNA is wrapped around histones, and, by transferring an acetyl group to the histones, genes can be turned on and off. In general, histone acetylation increases gene expression. In general, histone acetylation is linked to transcriptional activation and associated with euchromatin. Euchromatin, which is less densely compact, allows transcription factors to bind more easily to regulatory sites on DNA, causing transcriptional activation. When it was first discovered, it was thought that acetylation of lysine neutralizes the positive charge normally present, thus reducing affinity between histone and (negatively charged) DNA, which renders DNA more accessible to transcription factors. Research has emerged, since, to show that lysine acetylation and other posttranslational modifications of histo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRD7
Bromodomain-containing protein 7 is a protein that in humans is encoded by the ''BRD7'' gene. Interactions BRD7 has been shown to interact with IRF2 and HNRPUL1. Azoospermia BRD7 protein is a transcription regulator that is normally highly expressed in the testis, particularly in meiotic pachytene and diplotene spermatocytes and in round spermatids. However, in the testes of patients exhibiting spermatogenesis arrest and azoospermia, BRD7 protein expression is observed to be absent or reduced. Homozygous knockout mice RD7(-/-)are infertile and have increased DNA damage and apoptosis in their germline In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They .... References External links * Further reading * * * * * * * * * * * * * * * * {{refend [Baidu] |
BRD3
Bromodomain-containing protein 3 (BRD3) also known as RING3-like protein (RING3L) is a protein that in humans is encoded by the BRD3 gene. This gene was identified based on its homology to the gene encoding the RING3 (BRD2) protein, a serine/threonine kinase. The gene maps to 9q34, a region which contains several major histocompatibility complex (MHC) genes. Structure BRD3 is a member of the Bromodomain and Extra-Terminal motif (BET) protein family. Like other BET family members it contains two tandem homologous bromodomains and an "Extra-Terminal" motif. BRD3, similar to BRD2, does not have a long C-terminal domain as BET family proteins BRD4 and BRDT do. Function Like other BET protein family members, BRD3 associates with acetylated lysine residues on histones and transcription factors. BRD3 has been implicated in nucleosome remodeling in the context of transcription. In addition, BRD3 has been shown to interact with RNA molecules and form protein-RNA aggregates. B ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRDT
Bromodomain testis-specific protein is a protein that in humans is encoded by the ''BRDT'' gene. It is a member of the Bromodomain and Extra-terminal motif (BET) protein family. BRDT is similar to the RING3 protein family. It possesses 2 bromodomain motifs and a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation. The bromodomain is found in proteins that regulate transcription. Two transcript variants encoding the same protein have been found for this gene. The use of three different mouse models (Brdt knock-out mice, mice expressing a non-functional Brdt and mice expressing a mutated Brdt lacking its first bromodomain) showed that Brdt drives a meiotic and post-meiotic gene expression program. It also controls the genome-wide post-meiotic genome reorganization that occurs after histone hyperacetylation in elongating spermatids. Model organisms Model organisms have been us ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRD2
Bromodomain-containing protein 2 is a protein that in humans is encoded by the ''BRD2'' gene. BRD2 is part of the Bromodomain and Extra-Terminal motif (BET) protein family that also contains BRD3, BRD4, and BRDT in mammals Early descriptions demonstrated that BRD2 gene product is a mitogen-activated kinase which localizes to the nucleus. The gene maps to the major histocompatibility complex (MHC) class II region on chromosome 6p21.3 but sequence comparison suggests that the protein is not involved in the immune response. Homology to the ''Drosophila'' gene female sterile homeotic suggests that this human gene may be part of a signal transduction pathway involved in growth control. Functions *BRD2 has been implicated in cancer. *BRD2 loss in mice causes obesity without diabetes for unknown reasons. *BRD2 may have functional overlap with close homolog BRD3. *BRD2 function is blocked by BET inhibitors. Interactions BRD2 has been shown to interact with E2F2, and many transcription ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ming-Ming Zhou
Ming-Ming Zhou, Ph.D., is an expert in structural and chemical biology, NMR spectroscopy and drug design. He is currently the Dr. Harold and Golden Lamport Professor and Chairman of the Department of Pharmacological Sciences and Co-Director of the Drug Discovery Institute at the Icahn School of Medicine at Mount Sinai and Mount Sinai Health System in New York City as well as Professor of Oncological Sciences. Zhou has published more than 180 research articles and is an inventor of 28 patents. His research has been funded by grants from federal, state and private research foundations including the National Institutes of Health, the National Science Foundation, the New York State Stem Cell Science, the Institute for the Study of Aging, the American Foundation for AIDS Research, the American Cancer Society, GlaxoSmithKline, the Michael J. Fox Foundation, the Samuel Waxman Cancer Research Foundation, and the Wellcome Trust. He serves on the board of directors at the New York Structural ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRD9
Bromodomain-containing protein 9 is a protein that in humans is encoded by the ''BRD9'' gene. Structure and interaction BRD9 contains a bromodomain. It is closely related to BRD7. BRD9 is present in some SWI/SNF ATPase remodeling complexes. Role in cancer The BRD9 gene is frequently present in variable copy number in lung cancer. Small molecule inhibition Small molecules capable of binding to the bromodomain of BRD9 have been developed. See also Bromodomain A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducin ... References Human proteins {{gene-5-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ASH1L
ASH1L (also called huASH1, ASH1, ASH1L1, ASH1-like, or KMT2H) is a histone-lysine N-methyltransferase enzyme encoded by the ASH1L gene located at chromosomal band 1q22. ASH1L is the human homolog of Drosophila Ash1 (absent, small, or homeotic-like). Gene Ash1 was discovered as a gene causing an imaginal disc mutant phenotype in Drosophila. Ash1 is a member of the trithorax-group (trxG) of proteins, a group of transcriptional activators that are involved in regulating Hox gene expression and body segment identity. Drosophila Ash1 interacts with trithorax to regulate ultrabithorax expression. The human ASH1L gene spans 227.5 kb on chromosome 1, band q22. This region is rearranged in a variety of human cancers such as leukemia, non-Hodgkin’s lymphoma, and some solid tumors. The gene is expressed in multiple tissues, with highest levels in brain, kidney, and heart, as a 10.5-kb mRNA transcript. Structure Human ASH1L protein is 2969 amino acids long with a molecular weight ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
All-α Protein Fold
In molecular biology, protein fold classes are broad categories of protein tertiary structure topology. They describe groups of proteins that share similar amino acid and secondary structure proportions. Each class contains multiple, independent protein superfamilies (i.e. are not necessarily evolutionarily related to one another). Generally recognised classes Four large classes of protein that are generally agreed upon by the two main structure classification databases (SCOP and CATH). all-α All-α proteins are a class of structural domains in which the secondary structure is composed entirely of α-helices, with the possible exception of a few isolated β-sheets on the periphery. Common examples include the bromodomain, the globin fold and the homeodomain fold. all-β All-β proteins are a class of structural domains in which the secondary structure is composed entirely of β-sheets, with the possible exception of a few isolated α-helices on the periphery. Common e ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
