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23S ribosomal RNA is the large ribosomal RNA component of the 50S large ribosomal subunit in bacteria and archaea. It forms much of the subunit's structural framework and the RNA-based environment of the peptidyl transferase center. The functional RNA is distinct from the DNA sequence from which it is transcribed: a genomic sequence record and a mature ribosomal component describe different physical molecules.^[ref]

Structural experiments with an archaeal large ribosomal subunit placed two substrate analogues against conserved regions of 23S ribosomal RNA. The absence of nearby protein side chains at the bond-forming position supported the conclusion that the ribosome is a ribozyme.^[ref]

The 23S label refers to a sedimentation coefficient, not 23 nucleotides. It must not be added as though it were a molecular mass: the 50S large ribosomal subunit contains 23S ribosomal RNA, 5S ribosomal RNA and ribosomal proteins, and its sedimentation depends on the assembled object's shape and resistance to motion.^[ref] Thus a measurement of an isolated RNA component and a measurement of the complete subunit need not carry the same S value.

The large ribosomal subunit is the ribosomal subunit containing the peptidyl transferase center, where peptide bonds are formed during biological translation. It contains ribosomal RNA and ribosomal proteins, and provides a ribosomal exit tunnel through which the growing polypeptide passes. The small ribosomal subunit organizes decoding of messenger RNA; synthesis requires coordination between both parts of the ribosome.^[ref]

For a reaction example, let one peptidyl-tRNA carry a chain of four amino acid residues and an incoming aminoacyl-tRNA carry one more. Peptidyl transfer produces a five-residue chain attached to the incoming transfer RNA. The existing chain is transferred and extended; the reaction does not join five free amino acids all at once. Subsequent movement of the ribosome prepares the complex for another elongation cycle.

A 2000 structural experiment examined an archaeal large ribosomal subunit and complexes containing two substrate analogues. The analogues contacted conserved 23S ribosomal RNA in the catalytic region, with no protein side-chain atoms within about 18 angstroms of the bond-forming position. This supported the identification of the ribosome as a ribozyme. The same study found that both RNA and proteins contribute to the ribosomal exit tunnel.^[ref] The structural evidence identifies the reaction environment; it does not make every chemical step or proton-transfer mechanism directly visible.

A substrate analogue is a molecule designed or recognized as resembling an enzyme's substrate in features relevant to binding or reaction. Resemblance may involve molecular shape, electric charge or the arrangement of reactive groups. An analogue need not reproduce every property of the natural substrate: it may bind without undergoing the same reaction, react at a different rate or stabilize a useful experimental complex.

For a conceptual example, suppose a natural substrate is recognized through two binding groups and transformed at a third group. An analogue retaining the recognition groups but replacing the reactive group could reveal how the active site holds the substrate. Observing binding would answer a recognition question; it would not establish the natural reaction rate. Nor does the word analogue alone guarantee competitive inhibition: that requires evidence about how the compound affects the enzyme under the tested conditions.

In a 2000 ribosome study, structures of the large ribosomal subunit bound to two substrate analogues located the peptidyl transferase center. Conserved 23S ribosomal RNA contacted the analogues, providing evidence about the chemical environment for peptide bond synthesis.^[ref] The experimental value lies in making a normally transient arrangement accessible to structural measurement; interpreting the natural substrate still requires attention to what the analogue preserves and changes.