PDBsum entry 1vqn

Ribosome

PDB id: 1vqn

Contents

Protein chains

237 a.a.

337 a.a.

246 a.a.

140 a.a.

172 a.a.

119 a.a.

29 a.a.

160 a.a.

142 a.a.

132 a.a.

145 a.a.

194 a.a.

186 a.a.

115 a.a.

143 a.a.

95 a.a.

150 a.a.

81 a.a.

119 a.a.

53 a.a.

65 a.a.

154 a.a.

82 a.a.

142 a.a.

73 a.a.

56 a.a.

46 a.a.

92 a.a.

70 a.a.

DNA/RNA

Metals

_SR ×114

_MG ×94

_NA ×75

_CL ×22

_CD ×5

__K ×2

Waters ×7616

References listed in PDB file

Key reference

Title

An induced-Fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-Trna.

Authors

T.M.Schmeing, K.S.Huang, S.A.Strobel, T.A.Steitz.

Ref.

Nature, 2005, 438, 520-524. [DOI no: 10.1038/nature04152]

PubMed id

16306996

Abstract

The large ribosomal subunit catalyses the reaction between the alpha-amino group of the aminoacyl-tRNA bound to the A site and the ester carbon of the peptidyl-tRNA bound to the P site, while preventing the nucleophilic attack of water on the ester, which would lead to unprogrammed deacylation of the peptidyl-tRNA. Here we describe three new structures of the large ribosomal subunit of Haloarcula marismortui (Hma) complexed with peptidyl transferase substrate analogues that reveal an induced-fit mechanism in which substrates and active-site residues reposition to allow the peptidyl transferase reaction. Proper binding of an aminoacyl-tRNA analogue to the A site induces specific movements of 23S rRNA nucleotides 2618-2620 (Escherichia coli numbering 2583-2585) and 2541(2506), thereby reorienting the ester group of the peptidyl-tRNA and making it accessible for attack. In the absence of the appropriate A-site substrate, the peptidyl transferase centre positions the ester link of the peptidyl-tRNA in a conformation that precludes the catalysed nucleophilic attack by water. Protein release factors may also function, in part, by inducing an active-site rearrangement similar to that produced by the A-site aminoacyl-tRNA, allowing the carbonyl group and water to be positioned for hydrolysis.

Figure 2.
Figure 2: Steric exclusion of water results in protection of peptidyl-tRNA from deacylation in the uninduced state. When the peptidyl transferase centre is not in the induced state, as occurs when ChPmn and CCApcb (green) are bound, the ribosome (orange surface) occludes water from positions that could attack the ester group. Theoretical water molecules (red spheres), are shown aligned for attack at 105° to the plane of the ester group, 2.8 Å away from the ester carbon. Steric clashes with A2486(2451) and C2104(2063) block the position on one side, whereas the uninduced conformation of U2620(2585) would block the other side.

Figure 4.
Figure 4: Pre-attack conformation of the substrates. The hydroxyl group representing the -amino group of the A-site substrate, CChPmn (purple) is in position to attack the ester group of the P-site substrate CCApcb (green). It is within hydrogen-bonding distance of N3 of A2486(2451) and the 2' hydroxyl group of the P-site substrate. In this ground state, the reactive groups are 3.7 Å apart.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2005, 438, 520-524) copyright 2005.

Secondary reference #1

Title

Structural insights into the roles of water and the 2' Hydroxyl of the p site tRNA in the peptidyl transferase reaction.

Authors

T.M.Schmeing, K.S.Huang, D.E.Kitchen, S.A.Strobel, T.A.Steitz.

Ref.

Mol Cell, 2005, 20, 437-448. [DOI no: 10.1016/j.molcel.2005.09.006]

PubMed id

16285925

Figure 1.
Figure 1. Unbiased F[o] − F[c] Electron Density Maps for Some of the Complexes of the 50S Subunit Bound with Peptidyl Transferase Ligands, All Contoured at 3 σ

Figure 6.
Figure 6. The Reaction Pathway for Peptide Bond Formation

The above figures are reproduced from the cited reference with permission from Cell Press