6edd: Difference between revisions
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==Crystal structure of a GNAT Superfamily PA3944 acetyltransferase in complex with CoA (P1 space group)== | ==Crystal structure of a GNAT Superfamily PA3944 acetyltransferase in complex with CoA (P1 space group)== | ||
<StructureSection load='6edd' size='340' side='right' caption='[[6edd]], [[Resolution|resolution]] 1.55Å' scene=''> | <StructureSection load='6edd' size='340' side='right'caption='[[6edd]], [[Resolution|resolution]] 1.55Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6edd]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EDD OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6edd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EDD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EDD FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6edd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6edd OCA], [https://pdbe.org/6edd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6edd RCSB], [https://www.ebi.ac.uk/pdbsum/6edd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6edd ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ATSE3_PSEAE ATSE3_PSEAE] Catalyzes the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to an acceptor substrate and releases both CoA and the acetylated product. It prefers the peptide Asp-Phe methyl ester (or aspartame) and the peptide antibiotics polymyxin B and colistin. Other substrates like dopamine, serotonin, puromycin, chloramphenicol, D-glucosamine, glycine and N-alpha-acetyl-L-glutamine are used and displayed lower activity.<ref>PMID:23184347</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Deeper exploration of uncharacterized Gcn5-related N-acetyltransferases has the potential to expand our knowledge of the types of molecules that can be acylated by this important superfamily of enzymes and may offer new opportunities for biotechnological applications. While determining native or biologically relevant in vivo functions of uncharacterized proteins is ideal, their alternative or promiscuous in vitro capabilities provide insight into key active site interactions. Additionally, this knowledge can be exploited to selectively modify complex molecules and reduce byproducts when synthetic routes become challenging. During our exploration of uncharacterized Gcn5-related N-acetyltransferases from Pseudomonas aeruginosa, we identified such an example. We found that the PA3944 enzyme acetylates both polymyxin B and colistin on a single diaminobutyric acid residue closest to the macrocyclic ring of the antimicrobial peptide and determined the PA3944 crystal structure. This finding is important for several reasons: 1) to our knowledge this is the first report of enzymatic acylation of polymyxins and thus reveals a new type of substrate that this enzyme family can use, 2) the enzymatic acetylation offers a controlled method for antibiotic modification compared to classical promiscuous chemical methods, and 3) the site of acetylation would reduce the overall positive charge of the molecule, which is important for reducing nephrotoxic effects and may be a salvage strategy for this important class of antibiotics. While the physiological substrate for this enzyme remains unknown, our structural and functional characterization of PA3944 offers insight into its unique non-canonical substrate specificity. | |||
A Gcn5-related N-acetyltransferase (GNAT) capable of acetylating polymyxin B and colistin antibiotics in vitro.,Czub MP, Zhang B, Chiarelli MP, Majorek KA, Joe L, Porebski PJ, Revilla A, Wu W, Becker DP, Minor W, Kuhn ML Biochemistry. 2018 Nov 30. doi: 10.1021/acs.biochem.8b00946. PMID:30499668<ref>PMID:30499668</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6edd" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Czub | [[Category: Pseudomonas aeruginosa PAO1]] | ||
[[Category: Joachimiak | [[Category: Czub MP]] | ||
[[Category: Majorek | [[Category: Joachimiak A]] | ||
[[Category: Minor | [[Category: Majorek KA]] | ||
[[Category: Porebski | [[Category: Minor W]] | ||
[[Category: Satchell | [[Category: Porebski PJ]] | ||
[[Category: Satchell KJ]] | |||
Latest revision as of 09:23, 11 October 2023
Crystal structure of a GNAT Superfamily PA3944 acetyltransferase in complex with CoA (P1 space group)Crystal structure of a GNAT Superfamily PA3944 acetyltransferase in complex with CoA (P1 space group)
Structural highlights
FunctionATSE3_PSEAE Catalyzes the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to an acceptor substrate and releases both CoA and the acetylated product. It prefers the peptide Asp-Phe methyl ester (or aspartame) and the peptide antibiotics polymyxin B and colistin. Other substrates like dopamine, serotonin, puromycin, chloramphenicol, D-glucosamine, glycine and N-alpha-acetyl-L-glutamine are used and displayed lower activity.[1] Publication Abstract from PubMedDeeper exploration of uncharacterized Gcn5-related N-acetyltransferases has the potential to expand our knowledge of the types of molecules that can be acylated by this important superfamily of enzymes and may offer new opportunities for biotechnological applications. While determining native or biologically relevant in vivo functions of uncharacterized proteins is ideal, their alternative or promiscuous in vitro capabilities provide insight into key active site interactions. Additionally, this knowledge can be exploited to selectively modify complex molecules and reduce byproducts when synthetic routes become challenging. During our exploration of uncharacterized Gcn5-related N-acetyltransferases from Pseudomonas aeruginosa, we identified such an example. We found that the PA3944 enzyme acetylates both polymyxin B and colistin on a single diaminobutyric acid residue closest to the macrocyclic ring of the antimicrobial peptide and determined the PA3944 crystal structure. This finding is important for several reasons: 1) to our knowledge this is the first report of enzymatic acylation of polymyxins and thus reveals a new type of substrate that this enzyme family can use, 2) the enzymatic acetylation offers a controlled method for antibiotic modification compared to classical promiscuous chemical methods, and 3) the site of acetylation would reduce the overall positive charge of the molecule, which is important for reducing nephrotoxic effects and may be a salvage strategy for this important class of antibiotics. While the physiological substrate for this enzyme remains unknown, our structural and functional characterization of PA3944 offers insight into its unique non-canonical substrate specificity. A Gcn5-related N-acetyltransferase (GNAT) capable of acetylating polymyxin B and colistin antibiotics in vitro.,Czub MP, Zhang B, Chiarelli MP, Majorek KA, Joe L, Porebski PJ, Revilla A, Wu W, Becker DP, Minor W, Kuhn ML Biochemistry. 2018 Nov 30. doi: 10.1021/acs.biochem.8b00946. PMID:30499668[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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