|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6xxq' size='340' side='right'caption='[[6xxq]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='6xxq' size='340' side='right'caption='[[6xxq]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6xxq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XXQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XXQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6xxq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XXQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XXQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SCM:SPECTINOMYCIN'>SCM</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]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6sxj|6sxj]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SCM:SPECTINOMYCIN'>SCM</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">spc, aad9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1351 "Enterococcus proteiformis" Thiercelin and Jouhaud 1903])</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=6xxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xxq OCA], [https://pdbe.org/6xxq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xxq RCSB], [https://www.ebi.ac.uk/pdbsum/6xxq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xxq ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Streptomycin_3''-adenylyltransferase Streptomycin 3''-adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.47 2.7.7.47] </span></td></tr> | + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6xxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xxq OCA], [http://pdbe.org/6xxq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xxq RCSB], [http://www.ebi.ac.uk/pdbsum/6xxq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xxq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/S3AD_ENTFL S3AD_ENTFL]] Mediates bacterial resistance to the antibiotics streptomycin and spectomycin. | + | [https://www.uniprot.org/uniprot/S9AD_ENTFL S9AD_ENTFL] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 25: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Enterococcus proteiformis thiercelin and jouhaud 1903]] | + | [[Category: Enterococcus faecalis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Streptomycin 3''-adenylyltransferase]] | + | [[Category: Kanchugal P S]] |
| - | [[Category: P, S Kanchugal]]
| + | [[Category: Selmer M]] |
| - | [[Category: Selmer, M]] | + | |
| - | [[Category: Antibiotic resistance]]
| + | |
| - | [[Category: Nucleotidyltransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
S9AD_ENTFL
Publication Abstract from PubMed
Spectinomycin is a ribosome-binding antibiotic that blocks the translocation step of translation. A prevalent resistance mechanism is the modification of the drug by aminoglycoside nucleotidyl transferase (ANT) enzymes of the spectinomycin-specific ANT (9) family or by the dual-specificity ANT(3") (9) family that also acts on streptomycin. We previously reported the structural mechanism of streptomycin modification by the ANT(3") (9) AadA from Salmonella enterica ANT (9) from Enterococcus faecalis adenylates the 9-hydroxyl of spectinomycin. We here present the first structures of spectinomycin bound to an ANT enzyme. Structures were solved for ANT (9) in apo form, in complex with ATP, spectinomycin and magnesium or in complex with only spectinomycin. ANT (9) shows similar overall structure as AadA with an N-terminal nucleotidyltransferase domain and a C-terminal alpha-helical domain. Spectinomycin binds close to the entrance of the interdomain cleft, while ATP is buried at the bottom. Upon drug binding, the C-terminal domain rotates by 14 degrees to close the cleft, allowing contacts of both domains with the drug. Comparison with AadA shows that spectinomycin specificity is explained by a straight alpha5 helix and a shorter alpha5-alpha6 loop that would clash with the larger streptomycin substrate. In the active site, we observe two magnesium ions, one of them in a previously un-observed position that may activate the 9-hydroxyl for deprotonation by the catalytic base Glu-86. The observed binding mode for spectinomycin suggests that also spectinamides and aminomethyl spectinomycins, recent spectinomycin analogues with expansions in position 4 of the C ring, will be subjected to modification by ANT (9) and ANT(3") (9) enzymes.
Structural recognition of spectinomycin by resistance enzyme ANT(9) from Enterococcus faecalis.,Kanchugal P S, Selmer M Antimicrob Agents Chemother. 2020 Apr 6. pii: AAC.00371-20. doi:, 10.1128/AAC.00371-20. PMID:32253216[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kanchugal P S, Selmer M. Structural recognition of spectinomycin by resistance enzyme ANT(9) from Enterococcus faecalis. Antimicrob Agents Chemother. 2020 Apr 6. pii: AAC.00371-20. doi:, 10.1128/AAC.00371-20. PMID:32253216 doi:http://dx.doi.org/10.1128/AAC.00371-20
|
