8e0s: Difference between revisions
New page: '''Unreleased structure''' The entry 8e0s is ON HOLD Authors: Berti, P.J., Junop, M.S., Grainger, R. Description: DAHP (3-deoxy-D-arabinoheptulosonate-7-phosphate) Synthase complexed w... |
No edit summary |
||
| (3 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==DAHP (3-deoxy-D-arabinoheptulosonate-7-phosphate) Synthase complexed with DAHP Oxime in unbound:(bound)2:unbound conformations== | |||
<StructureSection load='8e0s' size='340' side='right'caption='[[8e0s]], [[Resolution|resolution]] 1.65Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8e0s]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E0S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E0S 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]] 1.65Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=52L:DAHP+OXIME'>52L</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</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=8e0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e0s OCA], [https://pdbe.org/8e0s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e0s RCSB], [https://www.ebi.ac.uk/pdbsum/8e0s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e0s ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AROG_ECOLI AROG_ECOLI] Stereospecific condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) giving rise to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
alpha-Carboxyketose synthases, including 3-deoxy-d-arabinoheptulosonate 7-phosphate synthase (DAHPS), are long-standing targets for inhibition. They are challenging targets to create tight-binding inhibitors against, and inhibitors often display half-of-sites binding and partial inhibition. Half-of-sites inhibition demonstrates the existence of inter-subunit communication in DAHPS. We used X-ray crystallography and spatially resolved hydrogen-deuterium exchange (HDX) to reveal the structural and dynamic bases for inter-subunit communication in Escherichia coli DAHPS(Phe), the isozyme that is feedback-inhibited by phenylalanine. Crystal structures of this homotetrameric (dimer-of-dimers) enzyme are invariant over 91% of its sequence. Three variable loops make up 8% of the sequence and are all involved in inter-subunit contacts across the tight-dimer interface. The structures have pseudo-twofold symmetry indicative of inter-subunit communication across the loose-dimer interface, with the diagonal subunits B and C always having the same conformation as each other, while subunits A and D are variable. Spatially resolved HDX reveals contrasting responses to ligand binding, which, in turn, affect binding of the second substrate, erythrose-4-phosphate (E4P). The N-terminal peptide, M1-E12, and the active site loop that binds E4P, F95-K105, are key parts of the communication network. Inter-subunit communication appears to have a catalytic role in all alpha-carboxyketose synthase families and a regulatory role in some members. | |||
Role of Half-of-Sites Reactivity and Inter-Subunit Communications in DAHP Synthase Catalysis and Regulation.,Balachandran N, Grainger RA, Rob T, Liuni P, Wilson DJ, Junop MS, Berti PJ Biochemistry. 2022 Oct 18;61(20):2229-2240. doi: 10.1021/acs.biochem.2c00465., Epub 2022 Oct 5. PMID:36197914<ref>PMID:36197914</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Berti | <div class="pdbe-citations 8e0s" style="background-color:#fffaf0;"></div> | ||
[[Category: Grainger | |||
[[Category: Junop | ==See Also== | ||
*[[DAHP synthase 3D structures|DAHP synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli K-12]] | |||
[[Category: Large Structures]] | |||
[[Category: Berti PJ]] | |||
[[Category: Grainger R]] | |||
[[Category: Junop MS]] | |||
Latest revision as of 20:32, 18 October 2023
DAHP (3-deoxy-D-arabinoheptulosonate-7-phosphate) Synthase complexed with DAHP Oxime in unbound:(bound)2:unbound conformationsDAHP (3-deoxy-D-arabinoheptulosonate-7-phosphate) Synthase complexed with DAHP Oxime in unbound:(bound)2:unbound conformations
Structural highlights
FunctionAROG_ECOLI Stereospecific condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) giving rise to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP). Publication Abstract from PubMedalpha-Carboxyketose synthases, including 3-deoxy-d-arabinoheptulosonate 7-phosphate synthase (DAHPS), are long-standing targets for inhibition. They are challenging targets to create tight-binding inhibitors against, and inhibitors often display half-of-sites binding and partial inhibition. Half-of-sites inhibition demonstrates the existence of inter-subunit communication in DAHPS. We used X-ray crystallography and spatially resolved hydrogen-deuterium exchange (HDX) to reveal the structural and dynamic bases for inter-subunit communication in Escherichia coli DAHPS(Phe), the isozyme that is feedback-inhibited by phenylalanine. Crystal structures of this homotetrameric (dimer-of-dimers) enzyme are invariant over 91% of its sequence. Three variable loops make up 8% of the sequence and are all involved in inter-subunit contacts across the tight-dimer interface. The structures have pseudo-twofold symmetry indicative of inter-subunit communication across the loose-dimer interface, with the diagonal subunits B and C always having the same conformation as each other, while subunits A and D are variable. Spatially resolved HDX reveals contrasting responses to ligand binding, which, in turn, affect binding of the second substrate, erythrose-4-phosphate (E4P). The N-terminal peptide, M1-E12, and the active site loop that binds E4P, F95-K105, are key parts of the communication network. Inter-subunit communication appears to have a catalytic role in all alpha-carboxyketose synthase families and a regulatory role in some members. Role of Half-of-Sites Reactivity and Inter-Subunit Communications in DAHP Synthase Catalysis and Regulation.,Balachandran N, Grainger RA, Rob T, Liuni P, Wilson DJ, Junop MS, Berti PJ Biochemistry. 2022 Oct 18;61(20):2229-2240. doi: 10.1021/acs.biochem.2c00465., Epub 2022 Oct 5. PMID:36197914[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||