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| | ==Crystal structure of the substrate binding domain of E.coli DnaK in complex with a short apidaecin peptide== | | ==Crystal structure of the substrate binding domain of E.coli DnaK in complex with a short apidaecin peptide== |
| - | <StructureSection load='4e81' size='340' side='right' caption='[[4e81]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4e81' size='340' side='right'caption='[[4e81]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4e81]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E81 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E81 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4e81]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Apis_mellifera Apis mellifera] and [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=4E81 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E81 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dkx|1dkx]], [[1dky|1dky]], [[1dkz|1dkz]], [[3dpo|3dpo]], [[3dpp|3dpp]], [[3dpq|3dpq]], [[3qnj|3qnj]]</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=4e81 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e81 OCA], [https://pdbe.org/4e81 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e81 RCSB], [https://www.ebi.ac.uk/pdbsum/4e81 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e81 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b0014, dnaK, groP, grpF, JW0013, seg ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=4e81 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e81 OCA], [http://pdbe.org/4e81 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e81 RCSB], [http://www.ebi.ac.uk/pdbsum/4e81 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e81 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DNAK_ECOLI DNAK_ECOLI]] Plays an essential role in the initiation of phage lambda DNA replication, where it acts in an ATP-dependent fashion with the DnaJ protein to release lambda O and P proteins from the preprimosomal complex. DnaK is also involved in chromosomal DNA replication, possibly through an analogous interaction with the DnaA protein. Also participates actively in the response to hyperosmotic shock.[HAMAP-Rule:MF_00332] | + | [[https://www.uniprot.org/uniprot/DNAK_ECOLI DNAK_ECOLI]] Plays an essential role in the initiation of phage lambda DNA replication, where it acts in an ATP-dependent fashion with the DnaJ protein to release lambda O and P proteins from the preprimosomal complex. DnaK is also involved in chromosomal DNA replication, possibly through an analogous interaction with the DnaA protein. Also participates actively in the response to hyperosmotic shock.[HAMAP-Rule:MF_00332] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4e81" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4e81" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Apis mellifera]] |
| - | [[Category: Straeter, N]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Zahn, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Chaperone]] | + | [[Category: Straeter N]] |
| | + | [[Category: Zahn M]] |
| Structural highlights
Function
[DNAK_ECOLI] Plays an essential role in the initiation of phage lambda DNA replication, where it acts in an ATP-dependent fashion with the DnaJ protein to release lambda O and P proteins from the preprimosomal complex. DnaK is also involved in chromosomal DNA replication, possibly through an analogous interaction with the DnaA protein. Also participates actively in the response to hyperosmotic shock.[HAMAP-Rule:MF_00332]
Publication Abstract from PubMed
The emergence of multiple-drug-resistant (MDR) bacterial pathogens in hospitals (nosocomial infections) presents a global threat of growing importance, especially for Gram-negative bacteria with extended spectrum beta-lactamase (ESBL) or the novel New Delhi metallo-beta-lactamase 1 (NDM-1) resistance. Starting from the antibacterial peptide apidaecin 1b, we have optimized the sequence to treat systemic infections with the most threatening human pathogens, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. The lead compound Api88 enters bacteria without lytic effects at the membrane and inhibits chaperone DnaK at the substrate binding domain with a K(D) of 5 mumol/L. The Api88-DnaK crystal structure revealed that Api88 binds with a seven residue long sequence (PVYIPRP), in two different modes. Mice did not show any sign of toxicity when Api88 was injected four times intraperitoneally at a dose of 40 mg/kg body weight (BW) within 24 h, whereas three injections of 1.25 mg/kg BW and 5 mg/kg BW were sufficient to rescue all animals in lethal sepsis models using pathogenic E. coli strains ATCC 25922 and Neumann, respectively. Radioactive labeling showed that Api88 enters all organs investigated including the brain and is cleared through both the liver and kidneys at similar rates. In conclusion, Api88 is a novel, highly promising, 18-residue peptide lead compound with favorable in vitro and in vivo properties including a promising safety margin.
Api88 Is a Novel Antibacterial Designer Peptide To Treat Systemic Infections with Multidrug-Resistant Gram-Negative Pathogens.,Czihal P, Knappe D, Fritsche S, Zahn M, Berthold N, Piantavigna S, Muller U, Van Dorpe S, Herth N, Binas A, Kohler G, De Spiegeleer B, Martin LL, Nolte O, Strater N, Alber G, Hoffmann R ACS Chem Biol. 2012 May 17. PMID:22594381[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Czihal P, Knappe D, Fritsche S, Zahn M, Berthold N, Piantavigna S, Muller U, Van Dorpe S, Herth N, Binas A, Kohler G, De Spiegeleer B, Martin LL, Nolte O, Strater N, Alber G, Hoffmann R. Api88 Is a Novel Antibacterial Designer Peptide To Treat Systemic Infections with Multidrug-Resistant Gram-Negative Pathogens. ACS Chem Biol. 2012 May 17. PMID:22594381 doi:10.1021/cb300063v
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