9d2t
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of S. aureus Threonine deaminase regulatory domain== | |
| + | <StructureSection load='9d2t' size='340' side='right'caption='[[9d2t]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9d2t]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9D2T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9D2T FirstGlance]. <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]] 2.8Å</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=9d2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9d2t OCA], [https://pdbe.org/9d2t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9d2t RCSB], [https://www.ebi.ac.uk/pdbsum/9d2t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9d2t ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ILVA_STAA3 ILVA_STAA3] Catalyzes the anaerobic formation of alpha-ketobutyrate and ammonia from threonine in a two-step reaction. The first step involved a dehydration of threonine and a production of enamine intermediates (aminocrotonate), which tautomerizes to its imine form (iminobutyrate). Both intermediates are unstable and short-lived. The second step is the nonenzymatic hydrolysis of the enamine/imine intermediates to form 2-ketobutyrate and free ammonia. In the low water environment of the cell, the second step is accelerated by RidA (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In Staphylococcus aureus, the branched-chain amino acid biosynthetic pathway provides essential intermediates for membrane biosynthesis. Threonine deaminase (IlvA) is the first enzyme in the pathway, and isoleucine feedback-regulates the enzyme in Escherichia coli. These studies on E. coli IlvA (EcIlvA) introduced the concept of allosteric regulation. To investigate the regulation of S. aureus IlvA (SaIlvA), we first conducted additional studies on EcIlvA. The previously determined crystal structure of EcIlvA revealed a tetrameric assembly of protomers, each with catalytic and regulatory domains, but the structural basis of isoleucine regulation was not characterized. Here, we present the crystal structure of the EcIlvA regulatory domain bound to isoleucine, which reveals the isoleucine binding site and conformational changes that initiate at Phe352 and propagate 23 Angstrom across the domain. This suggests an allosteric pathway that extends to the active site of the adjacent protomer, mediating regulation across the protomer-protomer interface. The EcIlvA(F352A) mutant binds isoleucine but is feedback-resistant due to the absence of the initiating Phe352. In contrast, SaIlvA is not feedback-regulated by isoleucine and does not bind it. The structure of the SaIlvA regulatory domain reveals a different organization that lacks the isoleucine binding site. Other potential allosteric inhibitors of SaIlvA, including phospholipid intermediates, do not affect enzyme activity. We propose that the absence of feedback inhibition in SaIlvA is due to its role in membrane biosynthesis. These findings enhance our understanding of IlvA's allosteric regulation and offer opportunities for engineering feedback-resistant IlvA variants for biotechnological use. | ||
| - | + | Isoleucine binding and regulation of Escherichia coli and Staphylococcus aureus threonine dehydratase (IlvA).,Yun MD, Subramanian C, Miller K, Jackson P, Radka CD, Rock CO bioRxiv [Preprint]. 2025 Mar 28:2025.03.06.641827. doi: , 10.1101/2025.03.06.641827. PMID:40093177<ref>PMID:40093177</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9d2t" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Staphylococcus aureus]] | ||
| + | [[Category: Rock CO]] | ||
| + | [[Category: Yun M]] | ||
Current revision
Crystal structure of S. aureus Threonine deaminase regulatory domain
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