INHIBITORS OF RNA SYNTHESIS

Slides:



Advertisements
Similar presentations
IB Topics: DNA, Transcription, Translation
Advertisements

FROM GENE TO PROTEIN.
RNA: Structure & Synthesis By Amr S. Moustafa, M.D.; Ph.D.
RNA Synthesis (Transcription) By Amr S. Moustafa, M.D.; Ph.D.
2.7: Transcription & Translation
Cell Division, Genetics, Molecular Biology
Gene Expression and Control Part 2
Protein Synthesis Genome - the genetic information of an organism DNA – in most organisms carries the genes RNA – in some things, for example retroviruses.
Cell Division, Genetics, Molecular Biology
Review: Proteins and their function in the early stages of replication 1 = initiator proteins 2 = single strand binding proteins 3 = helicase 4.
13.3: RNA and Gene Expression
Transcription & Translation
1. Important Features a. DNA contains genetic template" for proteins.
DNA Past Paper Questions. 1. Draw as simple diagram of the molecular structure of DNA. 5 marks.
RNA (Ribonucleic acid)
RNA Ribonucleic Acid.
Transcription: Synthesizing RNA from DNA
Transcription Transcription- synthesis of RNA from only one strand of a double stranded DNA helix DNA  RNA(  Protein) Why is RNA an intermediate????
Chapter 26 - RNA Metabolism
Transcription transcription Gene sequence (DNA) recopied or transcribed to RNA sequence Gene sequence (DNA) recopied or transcribed to RNA sequence.
RNA synthesis:transcrition Transcription is the process of the synthesis RNA molecule.
google. com/search
Biology 10.1 How Proteins are Made:
* Review DNA replication & Transcription Transcription The synthesis of mRNA.
Protein Synthesis. DNA acts like an "instruction manual“ – it provides all the information needed to function the actual work of translating the information.
Protein Synthesis Transcription and Translation. The Central Dogma The information encoded with the DNA nucleotide sequence of a double helix is transferred.
By: Azreena (D11A005) & Nur Nabila (D11A027)
Chapter 10: Molecular Biology of Gene Expression Jones and Bartlett Publishers © 2005.
1 Genes and How They Work Chapter Outline Cells Use RNA to Make Protein Gene Expression Genetic Code Transcription Translation Spliced Genes – Introns.
RNA Metabolism Transcription - process by which DNA (genetic info) gets made into RNA (mRNA, rRNA, or tRNA) by an RNA polymerase mRNA - messenger RNA -
Gene Expression. Central Dogma Information flows from: DNA  RNA  Protein Exception: reverse transcriptase (retroviruses) RNA  DNA  RNA  Protein.
TRANSCRIPTION. NECESSARY COMPONENTS DNA matrix DNA-dependent RNA-polymerase АТP, GТP, CТP, UТP Мg ions.
Lecture 4: Transcription in Prokaryotes Chapter 6.
© 2005 Jones and Bartlett Publishers Chapter 18 How Genes Work and How Genes are Controlled.
Chapter 8 Section 8.4: DNA Transcription 1. Objectives SWBAT describe the relationship between RNA and DNA. SWBAT identify the three kinds of RNA and.
DNA Transcription and Translation Review. There are 3 types of RNA: Messenger RNA (mRNA) Ribosomal RNA (rRNA) Transfer RNA (tRNA)
1 RNA ( Ribonucleic acid ) Structure: Similar to that of DNA except: 1- it is single stranded polyunucleotide chain. 2- Sugar is ribose 3- Uracil is instead.
The flow of genetic information:
GENETICS A Conceptual Approach
Section 20.2 Gene Expression
Biochemistry Free For All
Key Concepts After RNA polymerase binds DNA with the help of other proteins, it catalyzes the production of an RNA molecule whose base sequence is complementary.
Protein synthesis DNA is the genetic code for all life. DNA literally holds the instructions that make all life possible. Even so, DNA does not directly.
Inhibitors of Transcription
Context Cell nucleus chromosome gene double helix.
Lecture 5. Transcription: DNA→RNA
Relationship between Genotype and Phenotype
Enzymes and their functions involved in DNA replication
Topic DNA.
Gene Expression : Transcription and Translation
RNA (Ribonucleic acid)
Chapter 10 How Proteins Are Made.
Relationship between Genotype and Phenotype
Transcription in Prokaryotic (Bacteria)
RNA: The other nucleic acid
Genes and How They Work Chapter 15
TRANSCRIPTION--- SYNTHESIS OF RNA
copyright cmassengale
(Transcription & Translation)
13.1: RNA & Transcription.
Protein Synthesis The genetic code – the sequence of nucleotides in DNA – is ultimately translated into the sequence of amino acids in proteins – gene.
Protein synthesis
Regulation of transcription Plant Biotechnology Lecture 2
Protein Synthesis The genetic code – the sequence of nucleotides in DNA – is ultimately translated into the sequence of amino acids in proteins – gene.
4/6 Objective: Explain the steps and key players in transcription.
Nucleic Acids and Proteins
Chapter 18 How Genes Work and How Genes are Controlled
Comparison Of DNA And RNA Synthesis in Prokaryotes and Eukaryotes
4/2 Objective: Explain the steps and key players in transcription.
Molecular biology (2) (Foundation Block).
Presentation transcript:

INHIBITORS OF RNA SYNTHESIS BY JAVARE GOWDA G N Substance binds to the enzyme and decrees the enzyme activity.

INTRODUCTION RNA polymerase ensures the transcription of the information contained in DNA from DNA to mRNA. The gene, fragment of DNA, is the informational unit. Transcription of DNA into mRNA is done in the presence of ATP, UTP, GTP and CTP through RNA-polymerase-DNA-dependent, which catalyzes the elongation of the chain. The activity of RNA polymerase is controlled by activator and repressor proteins.

Transcription Transfer of nucleotide language of DNA to the nucleotide language of RNA, with the replacement of T by U. The process been catalyzed by the enzyme DNA dependent RNA polymerase.

Functions and properties of RNA polymerase Weiss et al in the year 1959 It searches the DNA for initiation site It unwinds a DNA(just one turn) to produce single stranded DNA template. It select the correct ribonucleotide triphosphate and catalyses the formation of phosphodiester bond Molecular weight is 480000 It has four subunit α, β, β1 and σ. α, β, β1 constitutes the core enzyme. σ has no catalytic function but helps in the recognition of initiation site.

In eukaryotes there are three types of RNA polymerase RNA Polymerase 1: It synthesizes precursors of rRNA . RNA Polymerase 2: It synthesizes precursors of mRNA. RNA Polymerase 3: It synthesizes precursors of tRNA .

INHIBITORS OF RNA SYNTHESIS RNA synthesis(Transcription) involved in three steps Chain initiation Chain elongation Termination And only two compounds are involved synthesis the RNA molecule, namely DNA(Deoxy ribonucleic acid) and DNA dependent RNA polymerase(enzyme) also called RNA polymerase Inhibitors of RNA synthesis can acts on only DNA and RNA polymerase.

Inhibitors of RNA synthesis mainly categorized into two types based on the compound involved in RNA synthesis Type 1: Inhibitors interact with DNA dependent RNA polymerase and inhibit the RNA synthesis. Type 2: Inhibitors interact with DNA(Deoxy ribonucleic acid) and inhibit the RNA synthesis.

Type 1: Inhibitors interact with DNA dependent RNA polymerase and inhibit the RNA synthesis. The enzyme which transcribe DNA synthesizing RNA(DNA dependent RNA polymerase) have structural differences in eukaryotic and prokaryotic cells In Prokaryotic cells(Streptolydigin and Rifamycin) In Eukaryotic cells(α-amanitin) α-amanitin Rifamycin Streptolydigin

1.α-amanitin It is a highly toxic, cyclic octopeptide, isolated from poisonus fungus Amanita phalloides (Mushrooms) It is a member of Amatoxins It is also called deathcap mushroom. . Division of basidiomycota. Widespread in europe.

Chemical formula is C39H54N10O14S It also found in rats (0.1mg/kg ) It is potent inhibitor of RNA polymerase 2 in eukaryotes. It doesn’t inhibit RNA Poly1 and RNA Poly3 of eukaryotes and Bacterial RNA polymerase.

Mechanism behind this antibiotic is formation of multiple stereospecific hydrogen bonds. α-amanitin interacts with bridge helix in RNA polymerase 2. The addition of α-amanitin can reduce the rate of RNA polymerase2, Transcribing on DNA from several thousands to few nucleotides per minute. Binding of α-amanitin puts a constraint on its mobility, hence slowing down the translocation of the polymerase and the rate of synthesis of the RNA molecule It occurs in elongation process of transcription.

2.Rifamycin Rifamycins are a group of antibiotics that are synthesized either naturally by the organism Amycolatopsis rifamycinica or artificially. Subclass of the larger family of ansamycins

Chemical formula is C43H58N4O12. Rifamycins are particularly effective against mycobacteria, therefore used to treat tuberculosis, leprosy, and Mycobacterium ovium complex infections. It was first isolated in 1957 from a fermentation culture of Streptomyces mediterranei by two scientist named Piero Sensi & Maria teresa timbal.

It is a inhibitor of RNA polymerase, specifically inhibits the initiation step of RNA synthesis and it is also called potent inhibitor of chain initiation. It is a potent inhibitor of prokaryotic RNA polymerase and much work has been done to elucidate the mechanism of its action. Chain elongation in the transcription reaction is not affected by this antibiotic, but a step of initiation are inhibited. Trade NameRifamycinManufacturerBiochem PharmaceuticalUnit450mgTypeCapsule/ TabletQuantity10Price53.06

The antibacterial activity of rifamycins relies on the inhibition of bacterial RNA polymerase, this is due to high affinity of rifamycins for the prokaryotic RNA polymerase Rifamycins bound to RNA polymerase indicates that rifamycin blocks synthesis by causing strong steric clashes with the growing oligonucleotide. If the rifamycin binds the polymerase after the chain extension process has started, no inhibition is observed on the biosythesis. Rifamycin will not bind to eukaryotic RNA polymerase.

3.Streptolydigin Streptolydigin is an antibiotic that works by inhibiting chain elongation by binding to RNA polymerase, thus inhibiting RNA synthesis inside a cell. Streptolydigin inhibits bacterial RNA polymerase, but not eukaryotic RNA polymerase It has antibacterial activity against a number of gram positive bacteria. Streptolydigin-602.72

Only at high concentration of the drug is the initiation process affected, because the formation of the first phosphodiester bond is also inhibited. Its chemical formula is C32H44N2O9.

Type 2: Inhibitors interact with DNA(Deoxy ribonucleic acid) and inhibit the RNA synthesis. Below are the antibiotics interact with DNA and inhibit the RNA synthesis. Actinomycin D Chromomycin A3 Mithramycin A

1.Actinomycin D Actinomycin D is the most significant member of actinomycines, which are a class of polypeptide antitumor antibiotics isolated from soil bacteria of the genus streptomyces It is one of the anticancer drug, and has been used for many years(1954). Its chemical formula is C64H86N12O16.

Actinomycin D is chromopeptide with antibiotic activity. It contains two cyclic peptides bound to the chromophoric phenoxazone ring. It binds specifically to the minor groove of the DNA double helix, and thus prevents it from being a template for RNA synthesis. Its ability to inhibit growth of rapid dividing cells makes it a effective agent in cancer treatment.

2.Chromomycin A3 Chromomycin A3 is the Anthraquinone antibiotic. Its chemical formula is C57H82O26. Its soluble in ethanol and DMSO (dimethylsulfoxide) Chromomycin A3 binds to transcription factor SP1 & SP3 of DNA to inhibit RNA synthesis.

3.Mithramycin A Similar to chromomycin A3 in structure and mechanism of action. Its chemical formula is C52H76O24.

Mithramycin A is a DNA-binding, anti-tumor and neuroprotective antibiotic originally isolated from Streptomyces plicatus. Mithramycin A binds to GC rich DNA sequences, displacing Sp1 transcription factor binding to oncogene promoters, which inhibits their expression.

References Sobell.H.M 1985, Actinomycin and DNA transcription. Meinhofer & Atherton 1977. Advantage and application of Microbiology PG no 16. Goldberg.I.H &Friedman.P.A. 1971. Annual review of Biochemistry volume 40. Freidberg.C. 2004. Current opinion in microbiology 7. Robert.F.Weaver 2009. Molecular biology 4th edition.