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| | ==Crystal Structure of Burkholderia cenocepacia HldA in Complex with an ATP-competitive Inhibitor== | | ==Crystal Structure of Burkholderia cenocepacia HldA in Complex with an ATP-competitive Inhibitor== |
| - | <StructureSection load='4e8w' size='340' side='right' caption='[[4e8w]], [[Resolution|resolution]] 2.87Å' scene=''> | + | <StructureSection load='4e8w' size='340' side='right'caption='[[4e8w]], [[Resolution|resolution]] 2.87Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4e8w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Burcj Burcj]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E8W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E8W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4e8w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_cenocepacia_J2315 Burkholderia cenocepacia J2315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E8W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IHA:{[2-({[5-(2,6-DIMETHOXYPHENYL)-1,2,4-TRIAZIN-3-YL]AMINO}METHYL)-1,3-BENZOTHIAZOL-5-YL]OXY}ACETIC+ACID'>IHA</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHA:{[2-({[5-(2,6-DIMETHOXYPHENYL)-1,2,4-TRIAZIN-3-YL]AMINO}METHYL)-1,3-BENZOTHIAZOL-5-YL]OXY}ACETIC+ACID'>IHA</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e84|4e84]], [[4e8z|4e8z]], [[4e8y|4e8y]]</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=4e8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e8w OCA], [https://pdbe.org/4e8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e8w RCSB], [https://www.ebi.ac.uk/pdbsum/4e8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e8w ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hldA, BceJ2315_28810, BCAL2945 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=216591 BURCJ])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4e8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e8w OCA], [http://pdbe.org/4e8w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e8w RCSB], [http://www.ebi.ac.uk/pdbsum/4e8w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e8w ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [[https://www.uniprot.org/uniprot/B4EB35_BURCJ B4EB35_BURCJ]] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Burcj]] | + | [[Category: Burkholderia cenocepacia J2315]] |
| - | [[Category: Junop, M S]] | + | [[Category: Large Structures]] |
| - | [[Category: Lee, T W]] | + | [[Category: Junop MS]] |
| - | [[Category: Verhey, T B]] | + | [[Category: Lee T-W]] |
| - | [[Category: Beta-clasp dimerization region]]
| + | [[Category: Verhey TB]] |
| - | [[Category: Lps-heptose biosynthesis]] | + | |
| - | [[Category: Pfkb carbohydrate kinase]]
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| - | [[Category: Phosphorylation]]
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| - | [[Category: Transferase-transferase inhibitor complex]]
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| Structural highlights
Function
[B4EB35_BURCJ]
Publication Abstract from PubMed
As an essential constituent of the outer membrane of Gram-negative bacteria, lipopolysaccharide contributes significantly to virulence and antibiotic resistance. The lipopolysaccharide biosynthetic pathway therefore serves as a promising therapeutic target for antivirulence drugs and antibiotic adjuvants. Here we report the structural-functional studies of d-glycero-beta-d-manno-heptose 7-phosphate kinase (HldA), an absolutely conserved enzyme in this pathway, from Burkholderia cenocepacia. HldA is structurally similar to members of the PfkB carbohydrate kinase family and appears to catalyze heptose phosphorylation via an in-line mechanism mediated mainly by a conserved aspartate, Asp270. Moreover, we report the structures of HldA in complex with two potent inhibitors in which both inhibitors adopt a folded conformation and occupy the nucleotide-binding sites. Together, these results provide important insight into the mechanism of HldA-catalyzed heptose phosphorylation and necessary information for further development of HldA inhibitors.
Structural-Functional Studies of Burkholderia cenocepaciad-Glycero-beta-d-manno-heptose 7-Phosphate Kinase (HldA) and Characterization of Inhibitors with Antibiotic Adjuvant and Antivirulence Properties.,Lee TW, Verhey TB, Antiperovitch PA, Atamanyuk D, Desroy N, Oliveira C, Denis A, Gerusz V, Drocourt E, Loutet SA, Hamad MA, Stanetty C, Andres SN, Sugiman-Marangos S, Kosma P, Valvano MA, Moreau F, Junop MS J Med Chem. 2013 Jan 22. PMID:23256532[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lee TW, Verhey TB, Antiperovitch PA, Atamanyuk D, Desroy N, Oliveira C, Denis A, Gerusz V, Drocourt E, Loutet SA, Hamad MA, Stanetty C, Andres SN, Sugiman-Marangos S, Kosma P, Valvano MA, Moreau F, Junop MS. Structural-Functional Studies of Burkholderia cenocepaciad-Glycero-beta-d-manno-heptose 7-Phosphate Kinase (HldA) and Characterization of Inhibitors with Antibiotic Adjuvant and Antivirulence Properties. J Med Chem. 2013 Jan 22. PMID:23256532 doi:10.1021/jm301483h
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