Symmetry at the active site of the ribosome: structural and functional implications

Agmon, Ilana; Bashan, Anat; Zarivach, Raz; Yonath, Ada

doi:10.1515/bc.2005.098

Cited by 113 publications

(184 citation statements)

References 44 publications

Supporting

Mentioning

167

Contrasting

Unclassified

Order By: Relevance

“…This ribosomal elaborate architectural design guides the process of peptide-bond reaction by forcing a rotational motion consistent with the 2-fold rotation axis. The bond connecting the universally conserved single-strand tRNA-3Ј end with the tRNA-acceptor stem of the A-site tRNA almost coincides with the symmetry axis, indicating that A-to P-site translocation involves two synchronized motions: an overall mRNA͞tRNA sideways shift and a rotation of the tRNA 3Јend (1)(2)(3). Guided by PTC components, the rotatory motion facilitates peptide-bond formation and nascent-chain elongation.…”

mentioning

confidence: 91%

“…Thus, the ribosome is a ribozyme exerting substrate positioning and promoting substratemediated catalysis (1)(2)(3)(4)(5).…”

mentioning

confidence: 99%

“…The symmetry-related region contains Ϸ180 nt and extends far beyond the PTC. It connects all functional centers involved in amino acid polymerization, including peptide-bond formation, the focus of this article (1)(2)(3). This ribosomal elaborate architectural design guides the process of peptide-bond reaction by forcing a rotational motion consistent with the 2-fold rotation axis.…”

mentioning

confidence: 99%

“…The nascent proteins are directed by the rotatory motion into the exit tunnel at extended conformation, fitting the tunnel's narrow opening. Hence, the ribosomal architecture provides all of the positional elements required for amino acid polymerization (2,3,9).…”

mentioning

confidence: 99%

See 3 more Smart Citations

The transition state for formation of the peptide bond in the ribosome

Gindulytė

Bashan

Agmon

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Using quantum mechanics and exploiting known crystallographic coordinates of tRNA substrate located in the ribosome peptidyl transferase center around the 2-fold axis, we have investigated the mechanism for peptide-bond formation. The calculation is based on a choice of 50 atoms assumed to be important in the mechanism. We used density functional theory to optimize the geometry and energy of the transition state (TS) for peptide-bond formation. The TS is formed simultaneously with the rotatory motion enabling the translocation of the A-site tRNA 3′ end into the P site, and we estimated the magnitude of rotation angle between the A-site starting position and the place at which the TS occurs. The calculated TS activation energy, E a , is 35.5 kcal (1 kcal = 4.18 kJ)/mol, and the increase in hydrogen bonding between the rotating A-site tRNA and ribosome nucleotides as the TS forms appears to stabilize it to a value qualitatively estimated to be ≈18 kcal/mol. The optimized geometry corresponds to a structure in which the peptide bond is being formed as other bonds are being broken, in such a manner as to release the P-site tRNA so that it may exit as a free molecule and be replaced by the translocating A-site tRNA. At TS formation the 2′ OH group of the P-site tRNA A76 forms a hydrogen bond with the oxygen atom of the carboxyl group of the amino acid attached to the A-site tRNA, which may be indicative of its catalytic role, consistent with recent biochemical experiments.

show abstract

mentioning

confidence: 91%

“…Thus, the ribosome is a ribozyme exerting substrate positioning and promoting substratemediated catalysis (1)(2)(3)(4)(5).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The transition state for formation of the peptide bond in the ribosome

Gindulytė

Bashan

Agmon

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…which may have evolved and emerged from an RNA world before a subsequent evolution into the modern protein/nucleic acid world, has been reported (1)(2)(3). In contemporary cells the ribosomes translate the genetic information (stored in the DNA) into proteins.…”

mentioning

confidence: 99%

Protoribosome by quantum kernel energy method

Huang

Krupkin

Bashan

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Experimental evidence suggests the existence of an RNA molecular prebiotic entity, called by us the "protoribosome," which may have evolved in the RNA world before evolution of the genetic code and proteins. This vestige of the RNA world, which possesses all of the capabilities required for peptide bond formation, seems to be still functioning in the heart of all of the contemporary ribosome. Within the modern ribosome this remnant includes the peptidyl transferase center. Its highly conserved nucleotide sequence is suggestive of its robustness under diverse environmental conditions, and hence on its prebiotic origin. Its twofold pseudosymmetry suggests that this entity could have been a dimer of self-folding RNA units that formed a pocket within which two activated amino acids might be accommodated, similar to the binding mode of modern tRNA molecules that carry amino acids or peptidyl moieties. Using quantum mechanics and crystal coordinates, this work studies the question of whether the putative protoribosome has properties necessary to function as an evolutionary precursor to the modern ribosome. The quantum model used in the calculations is density functional theory-B3LYP/3-21G*, implemented using the kernel energy method to make the computations practical and efficient. It occurs that the necessary conditions that would characterize a practicable protoribosome-namely (i) energetic structural stability and (ii) energetically stable attachment to substrates-are both well satisfied.bonding apparatus | puromycin | interaction energy | self-assembly | chemical model

show abstract

Sequence complementarity at the ribosomal Peptidyl Transferase Centre implies self‐replicating origin

Agmon

2017

FEBS Letters

Self Cite

View full text Add to dashboard Cite

A feasible scenario for the emergence of life requires the spontaneous materialization and sustainability of a proto-ribosome that could have catalysed the formation of the first peptides. Models of proto-ribosomes were derived from the ribosomal Peptidyl Transferase Centre (PTC) region, but the poor prebiotic copying abilities give rise to the question of their mode of replication. Here, complementarity is demonstrated in bacterial ribosomes, between nucleotides that constitute the two halves of the PTC cavity. The complementarity corroborates the dimeric nature of the proto-ribosome and is likely to underlie the symmetry of the PTC region. Furthermore, it indicates a simple and efficient replication mode; the strand of each monomer could have acted as a template for the synthesis of its counterpart, forming a self-replicating ribozyme.

show abstract

Symmetry at the active site of the ribosome: structural and functional implications

Cited by 113 publications

References 44 publications

The transition state for formation of the peptide bond in the ribosome

The transition state for formation of the peptide bond in the ribosome

Protoribosome by quantum kernel energy method

Sequence complementarity at the ribosomal Peptidyl Transferase Centre implies self‐replicating origin

Contact Info

Product

Resources

About