User:Wayne Decatur/Haloarcula Large Ribosomal Subunit: Difference between revisions

Then I realized that on addition to CCA-puromycin I need sidechains and bases from a few amino acids and nts near to or interacting with the Yarus analog so I added that to the unzipped version of [[Image:1s72simplified.PDB.gz|file]]  that I have been ussing and added back all the atoms from to the two nts that pair with the Yarus analog and 2486 [e.c. #2451) that is close to tetrahedral atom and the sidechains close to the Yarus analog. This file is uploaded at [1s72ALPHACplusccapurowithCERTAINSIDECHAINS.PDB] and despite the fact it doesn't have a .gz extension, IT IS GZIPPED. I had forgotten at first and uploaded the wrong one the first time.-->

 

:*It is important to note that two stalks (the L1 stalk and L7/L12 stalk) seen in lower resolution structures on each side of the large ribosomal subunit at lower resolution <ref>PMID: 9657144</ref> are not visible in the higher resolution structure viewed here. Thus, ''in actuality'' the Haloarcula large subunit has a less monolithic appearance with protuberances on either side of the central protuberance, yet clearly not possessing the distinct domains formed by the distinct rRNA domains visible in the secondary structure (see below).

::*<small>Helix 69 is a portion of Domain IV (See the location in [http://people.biochem.umass.edu/fournierlab/3dmodmap/hmarlsu2dframes.php the secondary structure]) and is part of one of the important conserved intersubunit bridges of the ribosome (b2a), although '''it is not visible in this structure'''. (The 13-nt stem-loop not seen would connect the highlighted spheres <scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72rrnadomain4h69/2'>here</scene>).) See the [[ribosome]] to see a structure where helix 69 is observed in the solved structure, extending from the large subunit under the A- and P- site tRNAs in the 70S ribosome and contacting the tRNAs and the small subunit decoding center. Helix 69 plays a roles in initiation, termination, and disassembly of the ribosome post-termination</small><ref>PMID: 17996252</ref><ref>PMID: 19007789</ref><ref>PMID: 16973438</ref>.

::*<font color="red">Domain V</font> lies at the core of the subunit. &nbsp; It is known to be intimately associated with the peptidyl transferase reaction that occurs during translation.

::*In addition to unliganded subunit, the large subunit structure has been solved with substrate analogs which provides a detailed view of the role <font color="red">domain V</font> plays in the chemistry of peptide bond synthesis. One of the analogs was the <font color="magenta">Yarus analog (CCA-puromycin)</font>, known to inhibit translation because it mimics normal substrate, specifically it resembles an unstable transition state intermediate involving both ends of the tRNAs and amino acid and formed during peptide bond synthesis. One atom in particular corresponds to the carbon of the tetrahedral carbon intermediate<ref>PMID: 10937990</ref>.

:::*<font color = "red">A2486</font> (E. coli #2451) of <font color = "red">Domain V</font> approaches the critical atom of the <font color="magenta">Yarus analog</font>.

===The ribosome is a ribozyme: Protein DOES NOT participate directly in the chemistry of peptide bond synthesis===

The chemistry of peptide bond synthesis is therefore not catalyzed by protein and in fact only RNA is in proximity to the site of peptide bond synthesis and thus the peptidyl transferase reaction is RNA-catalyzed and the ribosome is a ribozyme.

===Polypeptide Exit Tunnel===