Subunits TOPICAL

Despite the unity in secondary structural patterns, little is known about the three-dimensional, or tertiary, structure of rRNAs. Even less is known about the quaternary interactions that occur when ribosomal proteins combine with rRNAs and when the ensuing ribonucleoprotein complexes, the small and large subunits, come together to form the complete ribosome. Furthermore, assignments of functional roles to rRNA molecules are still tentative and approximate. (We return to these topics in Chapter 33.)... 

Bacitracin (Fig. 4) is a cyclic peptide antibiotic. The lipid II molecule involved in the bacterial cell wall biosynthesis has a C55 isoprenyl pyrophosphate moiety that must be dephosphorylated so that it can reparticipate in another round of lipid II transfer. Bacitracin binds to the isoprenyl pyrophosphate and prevents the dephosphorylation which, in turn, blocks cell wall growth by interfering with the release of the muropeptide subunits to the outside of the bacterial cell membrane. Bacitracin inhibits similar reactions in eukaryotic cells. So, it is systemically toxic but is an effective and widely used topical antibiotic. 

Dinuclear iron centres occur in several proteins. They either bind or activate dioxygen or they are hydrolases. Ribonucleotide reductase (RR) of the so-called class I type contains one such centre in the R2 protein in combination with a tyrosyl radical, both being essential for enzymatic activity which takes place in the R1 protein subunit. The diiron centre activates dioxygen to generate the tyrosyl radicals which in turn initiate the catalytic reaction in the R1 subunit. The interplay between the tyrosyl free radical in R2 and the formation of deoxyribonucleotides in R1 which also is proposed to involve a protein backbone radical is a topic of lively interest at present but is outside the scope of this review. Only a few recent references dealing with this aspect are mentioned without any further discussion.158 159 1 1,161... 

The preparation of (Me3Si)3SiM and derivatives thereof, which contain the iso-tetrasilabutyl subunit, is one of the best investigated topics in the chemistry of metalated oligosilanes. 

Chloramphenicol. Chloramphenicol (Chloromycetin) is a synthetically produced agent that exerts antibacterial effects similar to those of erythromycin that is, it binds to the 50S subunit of bacterial ribosomes and inhibits peptide bond formation. Chloramphenicol is a broad-spectrum antibiotic that is active against many gram-negative and gram-positive bacteria. This drug is administered systemically to treat serious infections such as typhoid fever, Haemophilus infections such as osteomyelitis, rickettsial infections such as Rocky Mountain spotted fever, and certain forms of meningitis. Chloramphenicol may also be administered topically to treat various skin, eye, and ear infections. 

Proteins containing more than one polypeptide chain, such as hemoglobin (see Topic B4), exhibit a fourth level of protein structure called quaternary structure (Fig. 8). This level of structure refers to the spatial arrangement of the polypeptide subunits and the nature of the interactions between them. These interactions may be covalent links (e.g. disulfide bonds) or noncovalent interactions (electrostatic forces, hydrogen bonding, hydrophobic interactions). 

An example of an enzyme which has different isoenzyme forms is lactate dehydrogenase (LDH) which catalyzes the reversible conversion of pyruvate into lactate in the presence of the coenzyme NADH (see above). LDH is a tetramer of two different types of subunits, called H and M, which have small differences in amino acid sequence. The two subunits can combine randomly with each other, forming five isoenzymes that have the compositions H4, H3M, H2M2, HM3 and M4. The five isoenzymes can be resolved electrophoretically (see Topic B8). M subunits predominate in skeletal muscle and liver, whereas H subunits predominate in the heart. H4 and H3M isoenzymes are found predominantly in the heart and red blood cells H2M2 is found predominantly in the brain and kidney while HM3 and M4 are found predominantly in the liver and skeletal muscle. Thus, the isoenzyme pattern is characteristic of a particular tissue, a factor which is of immense diagnostic importance in medicine. Myocardial infarction, infectious hepatitis and muscle diseases involve cell death of the affected tissue, with release of the cell contents into the blood. As LDH is a soluble, cytosolic protein it is readily released in these conditions. Under normal circumstances there is little LDH in the blood. Therefore the pattern of LDH isoenzymes in the blood is indicative of the tissue that released the isoenzymes and so can be used to diagnose a condition, such as a myocardial infarction, and to monitor the progress of treatment. 

In addition, allosteric enzymes may be controlled by effector molecules (activators and inhibitors) that bind to the enzyme at a site other than the active site (either on the same subunit or on a different subunit), thereby causing a change in the conformation of the active site which alters the rate of enzyme activity (cf. the binding of C02, H+ and 2,3-bisphosphoglycerate to hemoglobin see Topic B4). An allosteric activator increases the rate of enzyme activity, while an allosteric inhibitor decreases the activity of the enzyme. 

Each of the three eukaryotic RNA polymerases contains 12 or more subunits and so these are large complex enzymes. The genes encoding some of the subunits of each eukaryotic enzyme show DNA sequence similarities to genes encoding subunits of the core enzyme (a2PP ) of E. coli RNA polymerase (see Topic G2). However, four to seven other subunits of each eukaryotic RNA polymerase are unique in that they show no similarity either with bacterial RNA polymerase subunits or with the subunits of other eukaryotic RNA polymerases. 

The first codon translated in all mRNAs is AUG which codes for methionine. This AUG is called the start codon or initiation codon. Naturally, other AUG codons also occur internally in an mRNA where they encode methionine residues internal to the protein. Two different tRNAs are used for these two types of AUG codon tRNAfMet is used for the initiation codon and is called the initiator tRNA whereas tRNAmMet is used for internal AUG codons. In prokaryotes the first amino acid of a new protein is /V-formylmethionine (abbreviated fMet). Hence the aminoacyl-tRNA used in initiation is fMet-tRNAfMet. It is essential that the correct AUG is used as the initiation codon since this sets the correct reading frame for translation (see Topic HI). A short sequence rich in purines (5 -AGGAGGU-3 ), called the Shine-Dalgarno sequence, lies 5 to the AUG initiation codon (Fig. 3) and is complementary to part of the 16S rRNA in the small ribo-somal subunit. Therefore this is the binding site for the 30S ribosomal subunit... 

Peptide bond formation the second step, peptide bond formation, is catalyzed by peptidyl transferase, part of the large ribosomal subunit. In this reaction the carboxyl end of the amino acid bound to the tRNA in the P site is uncoupled from the tRNA and becomes joined by a peptide bond to the amino group of the amino acid linked to the tRNA in the A site (Fig. 5). A protein with peptidyl transferase activity has never been isolated. The reason is now clear in E. coli at least, the peptidyl transferase activity is associated with part of the 23S rRNA in the large ribosomal subunit. In other words, peptidyl transferase is a ribozyme, a catalytic activity that resides in an RNA molecule (see also Topic G9). 

Whereas a prokaryotic ribosome has a sedimentation coefficient (see Topic G9) of 70S and subunits of 30S and 50S, a eukaryotic ribosome has a sedimentation coefficient of 80S with subunits of 40S and 60S (see Topic G9). The composition of eukaryotic ribosomal subunits is also more complex than prokaryotic subunits (see Topic G9) but the function of each subunit is essentially the same as in prokaryotes. 

Phosphorylase exists in two interchangeable forms active phosphorylase a and a normally inactive phosphorylase b. Phosphorylase b is a dimer and is converted into phosphorylase a by phosphorylation of a single serine residue on each subunit by the enzyme phosphorylase kinase. The process can be reversed and phosphorylase inactivated by removal of the phosphate group by protein phosphatase I (Fig. 2a) (see Topic C5). 

These are sample activities of one particular subunit of the Water unit. Every subunit in the ABC series provides comparable occupation-specific activities for the topics under discussion. The ABC application exercises and activities have proven effective because they are realistic and are applicable to a broad range of students current and possible future lives outside the classroom (as consumers, family and community members, employees, and citizens). 

All chiral crown ethers incorporating one carbohydrate subunit possess two diastereo-topic faces of the macrocyclic ring. They are able to form diastereoisomeric complexes with primary alkylammonium cations. Since nonbonding interactions are responsible of the chiral recognition of optically active species, it would be desirable to form monofacial ligands in which the inclusion of a chiral molecule (or chiral ion) could proceed from the sterically hindered side only. This special molecular architecture may be followed by the fusion of the cryptand framework and the chiral unit. 

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