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{{Large structure}}
 
==The crystal structure of the large ribosomal subunit of Staphylococcus aureus in complex with lincomycin==
==The crystal structure of the large ribosomal subunit of Staphylococcus aureus in complex with lincomycin==
<StructureSection load='5hkv' size='340' side='right' caption='[[5hkv]], [[Resolution|resolution]] 3.66&Aring;' scene=''>
<StructureSection load='5hkv' size='340' side='right'caption='[[5hkv]], [[Resolution|resolution]] 3.66&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5hkv]] is a 27 chain structure with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_nctc_8325 Staphylococcus aureus subsp. aureus nctc 8325]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HKV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HKV FirstGlance]. <br>
<table><tr><td colspan='2'>[[5hkv]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_NCTC_8325 Staphylococcus aureus subsp. aureus NCTC 8325]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HKV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HKV FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3QB:LINCOMYCIN'>3QB</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=SPD:SPERMIDINE'>SPD</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.66&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wce|4wce]], [[4wfa|4wfa]], [[4wf9|4wf9]], [[4wfb|4wfb]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3QB:LINCOMYCIN'>3QB</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=SPD:SPERMIDINE'>SPD</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hkv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hkv OCA], [http://pdbe.org/5hkv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hkv RCSB], [http://www.ebi.ac.uk/pdbsum/5hkv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hkv ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5hkv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hkv OCA], [https://pdbe.org/5hkv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hkv RCSB], [https://www.ebi.ac.uk/pdbsum/5hkv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hkv ProSAT]</span></td></tr>
</table>
</table>
{{Large structure}}
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/RL16_STAA8 RL16_STAA8]] Binds 23S rRNA and is also seen to make contacts with the A and possibly P site tRNAs. [[http://www.uniprot.org/uniprot/RL6_STAA8 RL6_STAA8]] This protein binds to the 23S rRNA, and is important in its secondary structure. It is located near the subunit interface in the base of the L7/L12 stalk, and near the tRNA binding site of the peptidyltransferase center. [[http://www.uniprot.org/uniprot/RL22_STAA8 RL22_STAA8]] This protein binds specifically to 23S rRNA; its binding is stimulated by other ribosomal proteins, e.g. L4, L17, and L20. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome (By similarity).  The globular domain of the protein is located near the polypeptide exit tunnel on the outside of the subunit, while an extended beta-hairpin is found that lines the wall of the exit tunnel in the center of the 70S ribosome. [[http://www.uniprot.org/uniprot/RL23_STAA8 RL23_STAA8]] One of the early assembly proteins it binds 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the ribosome. Forms the main docking site for trigger factor binding to the ribosome. [[http://www.uniprot.org/uniprot/RL21_STAA8 RL21_STAA8]] This protein binds to 23S rRNA in the presence of protein L20. [[http://www.uniprot.org/uniprot/RL18_STAA8 RL18_STAA8]] This is one of the proteins that binds and probably mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance. [[http://www.uniprot.org/uniprot/RL5_STAA8 RL5_STAA8]] This is 1 of the proteins that binds and probably mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance. In the 70S ribosome it contacts protein S13 of the 30S subunit (bridge B1b), connecting the 2 subunits; this bridge is implicated in subunit movement. Contacts the P site tRNA; the 5S rRNA and some of its associated proteins might help stabilize positioning of ribosome-bound tRNAs. [[http://www.uniprot.org/uniprot/RL2_STAA8 RL2_STAA8]] One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial. Makes several contacts with the 16S rRNA in the 70S ribosome. [[http://www.uniprot.org/uniprot/RL14_STAA8 RL14_STAA8]] Binds to 23S rRNA. Forms part of two intersubunit bridges in the 70S ribosome. [[http://www.uniprot.org/uniprot/RL25_STAA3 RL25_STAA3]] This is one of the proteins that binds to the 5S RNA in the ribosome where it forms part of the central protuberance. [[http://www.uniprot.org/uniprot/RL19_STAA8 RL19_STAA8]] This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site. [[http://www.uniprot.org/uniprot/RL20_STAA8 RL20_STAA8]] Binds directly to 23S ribosomal RNA and is necessary for the in vitro assembly process of the 50S ribosomal subunit. It is not involved in the protein synthesizing functions of that subunit. [[http://www.uniprot.org/uniprot/RL13_STAA8 RL13_STAA8]] This protein is one of the early assembly proteins of the 50S ribosomal subunit, although it is not seen to bind rRNA by itself. It is important during the early stages of 50S assembly. [[http://www.uniprot.org/uniprot/RL3_STAA8 RL3_STAA8]] One of the primary rRNA binding proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit. [[http://www.uniprot.org/uniprot/RL24_STAA8 RL24_STAA8]] One of two assembly initiator proteins, it binds directly to the 5'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit.  One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. [[http://www.uniprot.org/uniprot/RL15_STAA8 RL15_STAA8]] Binds to the 23S rRNA. [[http://www.uniprot.org/uniprot/RL4_STAA8 RL4_STAA8]] One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome.  Forms part of the polypeptide exit tunnel.  
[https://www.uniprot.org/uniprot/RL2_STAA8 RL2_STAA8] One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial. Makes several contacts with the 16S rRNA in the 70S ribosome.
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Staphylococcus aureus subsp. aureus nctc 8325]]
[[Category: Large Structures]]
[[Category: Bashan, A]]
[[Category: Staphylococcus aureus subsp. aureus NCTC 8325]]
[[Category: Eyal, Z]]
[[Category: Bashan A]]
[[Category: Fridman, M]]
[[Category: Ben Hamou R]]
[[Category: Hamou, R Ben]]
[[Category: Eyal Z]]
[[Category: Matzov, D]]
[[Category: Fridman M]]
[[Category: Rozenberg, H]]
[[Category: Matzov D]]
[[Category: Yonath, A]]
[[Category: Rozenberg H]]
[[Category: Zimmerman, E]]
[[Category: Yonath A]]
[[Category: Antibiotic]]
[[Category: Zimmerman E]]
[[Category: Lincomycin]]
[[Category: Ribosome]]
[[Category: Rna]]

Latest revision as of 13:45, 16 August 2023

The crystal structure of the large ribosomal subunit of Staphylococcus aureus in complex with lincomycinThe crystal structure of the large ribosomal subunit of Staphylococcus aureus in complex with lincomycin

Structural highlights

5hkv is a 10 chain structure with sequence from Staphylococcus aureus subsp. aureus NCTC 8325. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.66Å
Ligands:, , , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RL2_STAA8 One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial. Makes several contacts with the 16S rRNA in the 70S ribosome.

Publication Abstract from PubMed

Antimicrobial resistance within a wide range of pathogenic bacteria is an increasingly serious threat to global public health. Among these pathogenic bacteria are the highly resistant, versatile and possibly aggressive bacteria, Staphylococcus aureus. Lincosamide antibiotics were proved to be effective against this pathogen. This small, albeit important group of antibiotics is mostly active against Gram-positive bacteria, but also used against selected Gram-negative anaerobes and protozoa. S. aureus resistance to lincosamides can be acquired by modifications and/or mutations in the rRNA and rProteins. Here, we present the crystal structures of the large ribosomal subunit of S. aureus in complex with the lincosamides lincomycin and RB02, a novel semisynthetic derivative and discuss the biochemical aspects of the in vitro potency of various lincosamides. These results allow better understanding of the drugs selectivity as well as the importance of the various chemical moieties of the drug for binding and inhibition.

Structural insights of lincosamides targeting the ribosome of Staphylococcus aureus.,Matzov D, Eyal Z, Benhamou RI, Shalev-Benami M, Halfon Y, Krupkin M, Zimmerman E, Rozenberg H, Bashan A, Fridman M, Yonath A Nucleic Acids Res. 2017 Sep 29;45(17):10284-10292. doi: 10.1093/nar/gkx658. PMID:28973455[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Matzov D, Eyal Z, Benhamou RI, Shalev-Benami M, Halfon Y, Krupkin M, Zimmerman E, Rozenberg H, Bashan A, Fridman M, Yonath A. Structural insights of lincosamides targeting the ribosome of Staphylococcus aureus. Nucleic Acids Res. 2017 Sep 29;45(17):10284-10292. doi: 10.1093/nar/gkx658. PMID:28973455 doi:http://dx.doi.org/10.1093/nar/gkx658

5hkv, resolution 3.66Å

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