4evy: Difference between revisions
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<StructureSection load='4evy' size='340' side='right' caption='[[4evy]], [[Resolution|resolution]] 1.77Å' scene=''> | <StructureSection load='4evy' size='340' side='right' caption='[[4evy]], [[Resolution|resolution]] 1.77Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4evy]] is a 2 chain structure | <table><tr><td colspan='2'>[[4evy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EVY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EVY FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TOY:TOBRAMYCIN'>TOY</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TOY:TOBRAMYCIN'>TOY</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aminoglycoside_N(6')-acetyltransferase Aminoglycoside N(6')-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.82 2.3.1.82] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aminoglycoside_N(6')-acetyltransferase Aminoglycoside N(6')-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.82 2.3.1.82] </span></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=4evy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4evy OCA], [http://pdbe.org/4evy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4evy RCSB], [http://www.ebi.ac.uk/pdbsum/4evy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4evy ProSAT]</span></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=4evy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4evy OCA], [http://pdbe.org/4evy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4evy RCSB], [http://www.ebi.ac.uk/pdbsum/4evy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4evy ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Modification of aminoglycosides by N-acetyltransferases (AACs) is one of the major mechanisms of resistance to these antibiotics in human bacterial pathogens. More than fifty enzymes belonging to the AAC(6') subfamily have been identified in Gram-negative and Gram-positive clinical isolates. Our understanding of the molecular function and evolutionary origin of these resistance enzymes remains incomplete. Here we report the structural and enzymatic characterization of AAC(6')-Ig and AAC(6')-Ih from Acinetobacter spp. The crystal structure of AAC(6')-Ig in complex with tobramycin revealed a large substrate-binding cleft remaining partially unoccupied by the substrate, which is in stark contrast with the previously characterized AAC(6')-Ib enzyme. Enzymatic analysis indicated that AAC(6')-Ig and -Ih possess a broad specificity against aminoglycosides but with significantly lower turnover rates as compared to other AAC(6') enzymes. Structure- and function-informed phylogenetic analysis of AAC(6') enzymes led to identification of at least three distinct subfamilies varying in oligomeric state, active site composition and drug recognition mode. Our data support the concept of AAC(6') functionality originating through convergent evolution from diverse Gcn5-related-N-acetyltransferase (GNAT) ancestral enzymes, with AAC(6')-Ig/Ih representing enzymes that may still retain ancestral non-resistance functions in the cell as provided by their particular active site properties. | |||
Structural and biochemical characterization of Acinetobacter spp. aminoglycoside acetyltransferases highlights functional and evolutionary variation among antibiotic resistance enzymes.,Stogios PJ, Kuhn ML, Evdokimova E, Law M, Courvalin P, Savchenko A ACS Infect Dis. 2016 Oct 27. PMID:27785912<ref>PMID:27785912</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4evy" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Anderson, W F]] | [[Category: Anderson, W F]] | ||
[[Category: Structural genomic]] | [[Category: Structural genomic]] | ||
Latest revision as of 22:37, 9 December 2016
Crystal structure of aminoglycoside antibiotic 6'-N-acetyltransferase AAC(6')-Ig from Acinetobacter haemolyticus in complex with tobramycinCrystal structure of aminoglycoside antibiotic 6'-N-acetyltransferase AAC(6')-Ig from Acinetobacter haemolyticus in complex with tobramycin
Structural highlights
Publication Abstract from PubMedModification of aminoglycosides by N-acetyltransferases (AACs) is one of the major mechanisms of resistance to these antibiotics in human bacterial pathogens. More than fifty enzymes belonging to the AAC(6') subfamily have been identified in Gram-negative and Gram-positive clinical isolates. Our understanding of the molecular function and evolutionary origin of these resistance enzymes remains incomplete. Here we report the structural and enzymatic characterization of AAC(6')-Ig and AAC(6')-Ih from Acinetobacter spp. The crystal structure of AAC(6')-Ig in complex with tobramycin revealed a large substrate-binding cleft remaining partially unoccupied by the substrate, which is in stark contrast with the previously characterized AAC(6')-Ib enzyme. Enzymatic analysis indicated that AAC(6')-Ig and -Ih possess a broad specificity against aminoglycosides but with significantly lower turnover rates as compared to other AAC(6') enzymes. Structure- and function-informed phylogenetic analysis of AAC(6') enzymes led to identification of at least three distinct subfamilies varying in oligomeric state, active site composition and drug recognition mode. Our data support the concept of AAC(6') functionality originating through convergent evolution from diverse Gcn5-related-N-acetyltransferase (GNAT) ancestral enzymes, with AAC(6')-Ig/Ih representing enzymes that may still retain ancestral non-resistance functions in the cell as provided by their particular active site properties. Structural and biochemical characterization of Acinetobacter spp. aminoglycoside acetyltransferases highlights functional and evolutionary variation among antibiotic resistance enzymes.,Stogios PJ, Kuhn ML, Evdokimova E, Law M, Courvalin P, Savchenko A ACS Infect Dis. 2016 Oct 27. PMID:27785912[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Anderson, W F
- Structural genomic
- Courvalin, P
- Evdokimova, E
- Minasov, G
- Savchenko, A
- Stogios, P J
- Yim, V
- Acetyl coenzyme some
- Antibiotic resistance
- Gcn5-related n-acetyltransferase superfamily
- Gnat superfamily
- Intracellular
- N-acetyltransferase fold
- National institute of allergy and infectious disease
- Niaid
- Transferase-antibiotic complex