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| | <StructureSection load='2zp2' size='340' side='right'caption='[[2zp2]], [[Resolution|resolution]] 3.01Å' scene=''> | | <StructureSection load='2zp2' size='340' side='right'caption='[[2zp2]], [[Resolution|resolution]] 3.01Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zp2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"vibrio_subtilis"_ehrenberg_1835 "vibrio subtilis" ehrenberg 1835]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZP2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zp2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZP2 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">kipI ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1423 "Vibrio subtilis" Ehrenberg 1835])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.01Å</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=2zp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zp2 OCA], [https://pdbe.org/2zp2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zp2 RCSB], [https://www.ebi.ac.uk/pdbsum/2zp2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zp2 ProSAT]</span></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=2zp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zp2 OCA], [https://pdbe.org/2zp2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zp2 RCSB], [https://www.ebi.ac.uk/pdbsum/2zp2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zp2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/KIPI_BACSU KIPI_BACSU]] Is a potent inhibitor of the autophosphorylation reaction of kinase A and its reverse reaction, but does not inhibit phosphate transfer to the Spo0F response regulator once kinase A is phosphorylated. KipI is an inhibitor of the catalytic domain of kinase A affecting the ATP/ADP reactions and not the phosphotransferase functions of this domain. The inhibition is noncompetitive with respect to ATP.
| + | [https://www.uniprot.org/uniprot/PXPB_BACSU PXPB_BACSU] Catalyzes the cleavage of 5-oxoproline to form L-glutamate coupled to the hydrolysis of ATP to ADP and inorganic phosphate (PubMed:28830929). In addition, is a potent inhibitor of the autophosphorylation reaction of kinase A (kinA) and its reverse reaction, but does not inhibit phosphate transfer to the Spo0F response regulator once kinase A is phosphorylated. Is an inhibitor of the catalytic domain of kinase A affecting the ATP/ADP reactions and not the phosphotransferase functions of this domain. The inhibition is non-competitive with respect to ATP (PubMed:9334321).<ref>PMID:28830929</ref> <ref>PMID:9334321</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Vibrio subtilis ehrenberg 1835]] | + | [[Category: Bacillus subtilis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jacques, D A]] | + | [[Category: Jacques DA]] |
| - | [[Category: Langley, D B]] | + | [[Category: Langley DB]] |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Histidine kinase inhibitor]]
| + | |
| - | [[Category: Kipi]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Protein kinase inhibitor]]
| + | |
| - | [[Category: Sporulation]]
| + | |
| - | [[Category: Transferase inhibitor]]
| + | |
| Structural highlights
Function
PXPB_BACSU Catalyzes the cleavage of 5-oxoproline to form L-glutamate coupled to the hydrolysis of ATP to ADP and inorganic phosphate (PubMed:28830929). In addition, is a potent inhibitor of the autophosphorylation reaction of kinase A (kinA) and its reverse reaction, but does not inhibit phosphate transfer to the Spo0F response regulator once kinase A is phosphorylated. Is an inhibitor of the catalytic domain of kinase A affecting the ATP/ADP reactions and not the phosphotransferase functions of this domain. The inhibition is non-competitive with respect to ATP (PubMed:9334321).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The sensor histidine kinase A (KinA) from Bacillus subtilis triggers a phosphorelay that activates sporulation. The antikinase KipI prevents sporulation by binding KinA and inhibiting the autophosphorylation reaction. Using neutron contrast variation, mutagenesis, and fluorescence data, we show that two KipI monomers bind via their C-domains at a conserved proline in the KinA dimerization and histidine-phosphotransfer (DHp) domain. Our crystal structure of the KipI C-domain reveals the binding motif has a distinctive hydrophobic groove formed by a five-stranded antiparallel beta-sheet; a characteristic of the cyclophilin family of proteins that bind prolines and often act as cis-trans peptidyl-prolyl isomerases. We propose that the DHp domain of KinA transmits conformational signals to regulate kinase activity via this proline-mediated interaction. Given that both KinA and KipI homologues are widespread in the bacterial kingdom, this mechanism has broad significance in bacterial signal transduction.
Histidine kinase regulation by a cyclophilin-like inhibitor.,Jacques DA, Langley DB, Jeffries CM, Cunningham KA, Burkholder WF, Guss JM, Trewhella J J Mol Biol. 2008 Dec 12;384(2):422-35. Epub 2008 Sep 16. PMID:18823995[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Niehaus TD, Elbadawi-Sidhu M, de Crecy-Lagard V, Fiehn O, Hanson AD. Discovery of a widespread prokaryotic 5-oxoprolinase that was hiding in plain sight. J Biol Chem. 2017 Sep 29;292(39):16360-16367. doi: 10.1074/jbc.M117.805028. Epub , 2017 Aug 22. PMID:28830929 doi:http://dx.doi.org/10.1074/jbc.M117.805028
- ↑ Wang L, Grau R, Perego M, Hoch JA. A novel histidine kinase inhibitor regulating development in Bacillus subtilis. Genes Dev. 1997 Oct 1;11(19):2569-79. doi: 10.1101/gad.11.19.2569. PMID:9334321 doi:http://dx.doi.org/10.1101/gad.11.19.2569
- ↑ Jacques DA, Langley DB, Jeffries CM, Cunningham KA, Burkholder WF, Guss JM, Trewhella J. Histidine kinase regulation by a cyclophilin-like inhibitor. J Mol Biol. 2008 Dec 12;384(2):422-35. Epub 2008 Sep 16. PMID:18823995 doi:10.1016/j.jmb.2008.09.017
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