4ab7: Difference between revisions
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< | ==Crystal structure of a tetrameric acetylglutamate kinase from Saccharomyces cerevisiae complexed with its substrate N- acetylglutamate== | ||
<StructureSection load='4ab7' size='340' side='right'caption='[[4ab7]], [[Resolution|resolution]] 3.25Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ab7]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AB7 FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.25Å</td></tr> | ||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NLG:N-ACETYL-L-GLUTAMATE'>NLG</scene></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=4ab7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ab7 OCA], [https://pdbe.org/4ab7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ab7 RCSB], [https://www.ebi.ac.uk/pdbsum/4ab7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ab7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ARG56_YEAST ARG56_YEAST] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
N-acetyl-L-glutamate kinase (NAGK) catalyzes the second, generally controlling, step of arginine biosynthesis. In yeasts, NAGK exists either alone or forming a metabolon with N-acetyl-L-glutamate synthase (NAGS), which catalyzes the first step and exists only within the metabolon. Yeast NAGK (yNAGK) has, in addition to the amino acid kinase (AAK) domain found in other NAGKs, a approximately 150-residue C-terminal domain of unclear significance belonging to the DUF619 domain family. We deleted this domain, proving that it stabilizes yNAGK, slows catalysis and modulates feed-back inhibition by arginine. We determined the crystal structures of both the DUF619 domain-lacking yNAGK, ligand-free as well as complexed with acetylglutamate or acetylglutamate and arginine, and of complete mature yNAGK. While all other known arginine-inhibitable NAGKs are doughnut-like hexameric trimers of dimers of AAK domains, yNAGK has as central structure a flat tetramer formed by two dimers of AAK domains. These dimers differ from canonical AAK dimers in the -110 degrees rotation of one subunit with respect to the other. In the hexameric enzymes, an N-terminal extension, found in all arginine-inhibitable NAGKs, forms a protruding helix that interlaces the dimers. In yNAGK, however, it conforms a two-helix platform that mediates interdimeric interactions. Arginine appears to freeze an open inactive AAK domain conformation. In the complete yNAGK structure, two pairs of DUF619 domains flank the AAK domain tetramer, providing a mechanism for the DUF619 domain modulatory functions. The DUF619 domain exhibits the histone acetyltransferase fold, resembling the catalytic domain of bacterial NAGS. However, the putative acetyl CoA site is blocked, explaining the lack of NAGS activity of yNAGK. We conclude that the tetrameric architecture is an adaptation to metabolon formation and propose an organization for this metabolon, suggesting that yNAGK may be a good model also for yeast and human NAGSs. | |||
Insight on an arginine synthesis metabolon from the tetrameric structure of yeast acetylglutamate kinase.,de Cima S, Gil-Ortiz F, Crabeel M, Fita I, Rubio V PLoS One. 2012;7(4):e34734. Epub 2012 Apr 18. PMID:22529931<ref>PMID:22529931</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
== | </div> | ||
[[ | <div class="pdbe-citations 4ab7" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Crabeel M]] | |||
[[Category: Crabeel | [[Category: Fita I]] | ||
[[Category: Fita | [[Category: Gil-Ortiz F]] | ||
[[Category: Gil-Ortiz | [[Category: Rubio V]] | ||
[[Category: Rubio | [[Category: De Cima S]] | ||
[[Category: | |||
Latest revision as of 14:23, 20 December 2023
Crystal structure of a tetrameric acetylglutamate kinase from Saccharomyces cerevisiae complexed with its substrate N- acetylglutamateCrystal structure of a tetrameric acetylglutamate kinase from Saccharomyces cerevisiae complexed with its substrate N- acetylglutamate
Structural highlights
FunctionPublication Abstract from PubMedN-acetyl-L-glutamate kinase (NAGK) catalyzes the second, generally controlling, step of arginine biosynthesis. In yeasts, NAGK exists either alone or forming a metabolon with N-acetyl-L-glutamate synthase (NAGS), which catalyzes the first step and exists only within the metabolon. Yeast NAGK (yNAGK) has, in addition to the amino acid kinase (AAK) domain found in other NAGKs, a approximately 150-residue C-terminal domain of unclear significance belonging to the DUF619 domain family. We deleted this domain, proving that it stabilizes yNAGK, slows catalysis and modulates feed-back inhibition by arginine. We determined the crystal structures of both the DUF619 domain-lacking yNAGK, ligand-free as well as complexed with acetylglutamate or acetylglutamate and arginine, and of complete mature yNAGK. While all other known arginine-inhibitable NAGKs are doughnut-like hexameric trimers of dimers of AAK domains, yNAGK has as central structure a flat tetramer formed by two dimers of AAK domains. These dimers differ from canonical AAK dimers in the -110 degrees rotation of one subunit with respect to the other. In the hexameric enzymes, an N-terminal extension, found in all arginine-inhibitable NAGKs, forms a protruding helix that interlaces the dimers. In yNAGK, however, it conforms a two-helix platform that mediates interdimeric interactions. Arginine appears to freeze an open inactive AAK domain conformation. In the complete yNAGK structure, two pairs of DUF619 domains flank the AAK domain tetramer, providing a mechanism for the DUF619 domain modulatory functions. The DUF619 domain exhibits the histone acetyltransferase fold, resembling the catalytic domain of bacterial NAGS. However, the putative acetyl CoA site is blocked, explaining the lack of NAGS activity of yNAGK. We conclude that the tetrameric architecture is an adaptation to metabolon formation and propose an organization for this metabolon, suggesting that yNAGK may be a good model also for yeast and human NAGSs. Insight on an arginine synthesis metabolon from the tetrameric structure of yeast acetylglutamate kinase.,de Cima S, Gil-Ortiz F, Crabeel M, Fita I, Rubio V PLoS One. 2012;7(4):e34734. Epub 2012 Apr 18. PMID:22529931[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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