|
|
| (4 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal structure of a GNAT superfamily acetyltransferase PA4794 in complex with CoA== | | ==Crystal structure of a GNAT superfamily acetyltransferase PA4794 in complex with CoA== |
| - | <StructureSection load='4kub' size='340' side='right' caption='[[4kub]], [[Resolution|resolution]] 1.57Å' scene=''> | + | <StructureSection load='4kub' size='340' side='right'caption='[[4kub]], [[Resolution|resolution]] 1.57Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kub]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KUB OCA]. <br> | + | <table><tr><td colspan='2'>[[4kub]] is a 1 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=4KUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KUB FirstGlance]. <br> |
| - | </td></tr><tr><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=SO4:SULFATE+ION'>SO4</scene><br> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.57Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pgp|3pgp]], [[4klv|4klv]], [[4klw|4klw]], [[4kor|4kor]], [[4kos|4kos]], [[4kot|4kot]], [[4kou|4kou]], [[4kov|4kov]], [[4kow|4kow]], [[4kox|4kox]], [[4koy|4koy]], [[4kua|4kua]]</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PA4794 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE])</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=4kub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kub OCA], [https://pdbe.org/4kub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kub RCSB], [https://www.ebi.ac.uk/pdbsum/4kub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kub ProSAT]</span></td></tr> |
| - | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> | + | </table> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4kub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kub OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kub RCSB], [http://www.ebi.ac.uk/pdbsum/4kub PDBsum]</span></td></tr> | + | == Function == |
| - | <table> | + | [https://www.uniprot.org/uniprot/Q9HV14_PSEAE Q9HV14_PSEAE] |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed == | + | |
| - | The Gcn5-related N-acetyltransferase (GNAT) superfamily is a large group of evolutionarily related acetyltransferases, with multiple paralogs in organisms from all kingdoms of life. The functionally characterized GNATs have been shown to catalyze the transfer of an acetyl group from acetyl-coenzyme A (AcCoA) to the amine of a wide range of substrates, including small molecules and proteins. GNATs are prevalent and implicated in a myriad of aspects of eukaryotic and prokaryotic physiology, but functions of many GNATs remain unknown. In this work, we used a multi-pronged approach of X-ray crystallography and biochemical characterization to elucidate the sequence-structure-function relationship of the GNAT superfamily member PA4794 from Pseudomonas aeruginosa. We determined that PA4794 acetylates the Nepsilon amine of a C-terminal lysine residue of a peptide, suggesting it is a protein acetyltransferase specific for a C-terminal lysine of a substrate protein or proteins. Further, we identified a number of molecules, including cephalosporin antibiotics, that are inhibitors of PA4794 and bind in its substrate-binding site. Often, these molecules mimic the conformation of the acetylated peptide product. We have determined structures of PA4794 in the apo-form, in complexes with AcCoA, CoA, several antibiotics and other small molecules, and a ternary complex with the products of the reaction: CoA and acetylated peptide. Also, we analyzed PA4794 mutants to identify residues important for substrate binding and catalysis.
| + | |
| - | | + | |
| - | Structural, functional and inhibition studies of a GNAT superfamily protein PA4794: a new C-terminal lysine protein acetyltransferase from Pseudomonas aeruginosa.,Majorek KA, Kuhn ML, Chruszcz M, Anderson WF, Minor W J Biol Chem. 2013 Sep 3. PMID:24003232<ref>PMID:24003232</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pseae]] | + | [[Category: Large Structures]] |
| - | [[Category: Chruszcz, M.]] | + | [[Category: Pseudomonas aeruginosa PAO1]] |
| - | [[Category: Joachimiak, A.]] | + | [[Category: Chruszcz M]] |
| - | [[Category: MCSG, Midwest Center for Structural Genomics.]] | + | [[Category: Joachimiak A]] |
| - | [[Category: Majorek, K A.]] | + | [[Category: Majorek KA]] |
| - | [[Category: Minor, W.]] | + | [[Category: Minor W]] |
| - | [[Category: Osinski, T.]] | + | [[Category: Osinski T]] |
| - | [[Category: Acetyltransferase]]
| + | |
| - | [[Category: Gnat]]
| + | |
| - | [[Category: Mcsg]]
| + | |
| - | [[Category: Midwest center for structural genomic]]
| + | |
| - | [[Category: Psi-biology]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| - | [[Category: Transferase]]
| + | |
