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Ribosomes are macromolecular machines, found within all cells, that perform biological protein synthesis. Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to form polypeptide chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA (rRNA) molecules and many ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.
In biology, translation is the process in living cells in which proteins are produced using RNA molecules as templates. The generated protein is a sequence of amino acids. This sequence is determined by the sequence of nucleotides in the RNA. The nucleotides are considered three at a time. Each such triple results in addition of one specific amino acid to the protein being generated. The matching from nucleotide triple to amino acid is called the genetic code. The translation is performed by a large complex of functional RNA and proteins called ribosomes. The entire process is called gene expression.
In molecular biology, biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism.
Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal DNA (rDNA) and then bound to ribosomal proteins to form small and large ribosome subunits. rRNA is the physical and mechanical factor of the ribosome that forces transfer RNA (tRNA) and messenger RNA (mRNA) to process and translate the latter into proteins. Ribosomal RNA is the predominant form of RNA found in most cells; it makes up about 80% of cellular RNA despite never being translated into proteins itself. Ribosomes are composed of approximately 60% rRNA and 40% ribosomal proteins by mass.
Bacterial translation is the process by which messenger RNA is translated into proteins in bacteria.
Eukaryotic translation is the biological process by which messenger RNA is translated into proteins in eukaryotes. It consists of four phases: initiation, elongation, termination, and recapping.
Aminoacyl-tRNA is tRNA to which its cognate amino acid is chemically bonded (charged). The aa-tRNA, along with particular elongation factors, deliver the amino acid to the ribosome for incorporation into the polypeptide chain that is being produced during translation.
EF-Tu is a prokaryotic elongation factor responsible for catalyzing the binding of an aminoacyl-tRNA (aa-tRNA) to the ribosome. It is a G-protein, and facilitates the selection and binding of an aa-tRNA to the A-site of the ribosome. As a reflection of its crucial role in translation, EF-Tu is one of the most abundant and highly conserved proteins in prokaryotes. It is found in eukaryotic mitochondria as TUFM.
Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids (anabolism), and the breakdown of proteins by catabolism.
50S is the larger subunit of the 70S ribosome of prokaryotes, i.e. bacteria and archaea. It is the site of inhibition for antibiotics such as macrolides, chloramphenicol, clindamycin, and the pleuromutilins. It includes the 5S ribosomal RNA and 23S ribosomal RNA.
The 23S rRNA is a 2,904 nucleotide long component of the large subunit (50S) of the bacterial/archean ribosome and makes up the peptidyl transferase center (PTC). The 23S rRNA is divided into six secondary structural domains titled I-VI, with the corresponding 5S rRNA being considered domain VII. The ribosomal peptidyl transferase activity resides in domain V of this rRNA, which is also the most common binding site for antibiotics that inhibit translation, making it a target for ribosomal engineering. A well-known member of this antibiotic class, chloramphenicol, acts by inhibiting peptide bond formation, with recent 3D-structural studies showing two different binding sites depending on the species of ribosome. Numerous mutations in domains of the 23S rRNA with Peptidyl transferase activity have resulted in antibiotic resistance. 23S rRNA genes typically have higher sequence variations, including insertions and/or deletions, compared to other rRNAs.
A protein synthesis inhibitor is a compound that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins.
Streptogramin A is a group of antibiotics within the larger family of antibiotics known as streptogramins. They are synthesized by the bacteria Streptomyces virginiae. The streptogramin family of antibiotics consists of two distinct groups: group A antibiotics contain a 23-membered unsaturated ring with lactone and peptide bonds while group B antibiotics are depsipeptides. While structurally different, these two groups of antibiotics act synergistically, providing greater antibiotic activity than the combined activity of the separate components. These antibiotics have until recently been commercially manufactured as feed additives in agriculture, although today there is increased interest in their ability to combat antibiotic-resistant bacteria, particularly vancomycin-resistant bacteria.
Streptogramin B is a subgroup of the streptogramin antibiotics family. These natural products are cyclic hexa- or hepta depsipeptides produced by various members of the genus of bacteria Streptomyces. Many of the members of the streptogramins reported in the literature have the same structure and different names; for example, pristinamycin IA = vernamycin Bα = mikamycin B = osteogrycin B.
Amino acid activation refers to the attachment of an amino acid to its respective transfer RNA (tRNA). The reaction occurs in the cell cytosol and consists of two steps: first, the enzyme aminoacyl tRNA synthetase catalyzes the binding of adenosine triphosphate (ATP) to a corresponding amino acid, forming a reactive aminoacyl adenylate intermediate and releasing inorganic pyrophosphate (PPi). Subsequently, aminoacyl tRNA synthetase binds the AMP-amino acid to a tRNA molecule, releasing AMP and attaching the amino acid to the tRNA. The resulting aminoacyl-tRNA is said to be charged.
The P-site is the second binding site for tRNA in the ribosome. The other two sites are the A-site (aminoacyl), which is the first binding site in the ribosome, and the E-site (exit), the third. During protein translation, the P-site holds the tRNA which is linked to the growing polypeptide chain. When a stop codon is reached, the peptidyl-tRNA bond of the tRNA located in the P-site is cleaved releasing the newly synthesized protein. During the translocation step of the elongation phase, the mRNA is advanced by one codon, coupled to movement of the tRNAs from the ribosomal A to P and P to E sites, catalyzed by elongation factor EF-G.
EF-P is an essential protein that in bacteria stimulates the formation of the first peptide bonds in protein synthesis. Studies show that EF-P prevents ribosomes from stalling during the synthesis of proteins containing consecutive prolines. EF-P binds to a site located between the binding site for the peptidyl tRNA and the exiting tRNA. It spans both ribosomal subunits with its amino-terminal domain positioned adjacent to the aminoacyl acceptor stem and its carboxyl-terminal domain positioned next to the anticodon stem-loop of the P site-bound initiator tRNA. The EF-P protein shape and size is very similar to a tRNA and interacts with the ribosome via the exit “E” site on the 30S subunit and the peptidyl-transferase center (PTC) of the 50S subunit. EF-P is a translation aspect of an unknown function, therefore It probably functions indirectly by altering the affinity of the ribosome for aminoacyl-tRNA, thus increasing their reactivity as acceptors for peptidyl transferase.
In molecular biology, VAR1 protein domain, otherwise known as variant protein 1, is a ribosomal protein that forms part of the small ribosomal subunit in yeast mitochondria. Mitochondria possess their own ribosomes responsible for the synthesis of a small number of proteins encoded by the mitochondrial genome. VAR1 is the only protein in the yeast mitochondrial ribosome to be encoded in the mitochondria - the remaining approximately 80 ribosomal proteins are encoded in the nucleus. VAR1 along with 15S rRNA are necessary for the formation of mature 37S subunits.
Ribosomal L28e protein family is a family of evolutionarily related proteins. Members include 60S ribosomal protein L28.
Bottromycin is a macrocyclic peptide with antibiotic activity. It was first discovered in 1957 as a natural product isolated from Streptomyces bottropensis. It has been shown to inhibit methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) among other Gram-positive bacteria and mycoplasma. Bottromycin is structurally distinct from both vancomycin, a glycopeptide antibiotic, and methicillin, a beta-lactam antibiotic.
References
- ↑ Tirumalai MR, Rivas M, Tran Q, Fox GE (November 2021). "The Peptidyl Transferase Center: a Window to the Past". Microbiol Mol Biol Rev. 85 (4): e0010421. doi:10.1128/MMBR.00104-21. PMC 8579967 . PMID 34756086.
- 1 2 Garrett RH, Grisham CM (2012). Biochemistry (5th ed.). Belmont CA: Brooks/Cole. ISBN 978-1-133-10629-6.
- ↑ "Peptidyl Transferase - Acyltransferases - Transferases - Enzymes - Products". www.axonmedchem.com. Retrieved 2018-11-10.
- 1 2 "Part Three: Gene Expression and Protein Synthesis". www.bx.psu.edu. Retrieved 2018-10-30.
- ↑ Moore PB, Steitz TA (February 2003). "After the ribosome structures: how does peptidyl transferase work?". RNA. 9 (2): 155–9. doi:10.1261/rna.2127103. PMC 1370378 . PMID 12554855.
- 1 2 3 Catalyst University, Peptidyl Transferase/Ribosome Physiology, Biochemistry, and Mechanism , retrieved 2018-10-07
- ↑ Gu Z, Harrod R, Rogers EJ, Lovett PS (June 1994). "Anti-peptidyl transferase leader peptides of attenuation-regulated chloramphenicol-resistance genes". Proceedings of the National Academy of Sciences of the United States of America. 91 (12): 5612–6. Bibcode:1994PNAS...91.5612G. doi: 10.1073/pnas.91.12.5612 . PMC 44046 . PMID 7515506.
- ↑ Long KS, Hansen LH, Jakobsen L, Vester B (April 2006). "Interaction of pleuromutilin derivatives with the ribosomal peptidyl transferase center". Antimicrobial Agents and Chemotherapy. 50 (4): 1458–62. doi:10.1128/AAC.50.4.1458-1462.2006. PMC 1426994 . PMID 16569865.
- ↑ Kaiser G. "Protein synthesis inhibitors: macrolides mechanism of action animation. Classification of agents". Pharmamotion. The Community College of Baltimore County. Archived from the original on December 26, 2008. Retrieved July 31, 2009.
