5dkp: Difference between revisions
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==Crystal Structure of N. meningitidis ClpP in complex with agonist ADEP A54556.== | ==Crystal Structure of N. meningitidis ClpP in complex with agonist ADEP A54556.== | ||
<StructureSection load='5dkp' size='340' side='right' caption='[[5dkp]], [[Resolution|resolution]] 2.38Å' scene=''> | <StructureSection load='5dkp' size='340' side='right'caption='[[5dkp]], [[Resolution|resolution]] 2.38Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5dkp]] is a 56 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DKP OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5dkp]] is a 56 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_meningitidis_MC58 Neisseria meningitidis MC58] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DKP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DKP FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.381Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MAA:N-METHYL-L-ALANINE'>MAA</scene>, <scene name='pdbligand=MP8:(4R)-4-METHYL-L-PROLINE'>MP8</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OTT:(2E,4E,6E)-OCTA-2,4,6-TRIENOIC+ACID'>OTT</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=5dkp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dkp OCA], [https://pdbe.org/5dkp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dkp RCSB], [https://www.ebi.ac.uk/pdbsum/5dkp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dkp ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/CLPP_NEIMB CLPP_NEIMB] Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins.[HAMAP-Rule:MF_00444] | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The problem of antibiotic resistance has prompted the search for new antibiotics with novel mechanisms of action. Analogues of the A54556 cyclic acyldepsipeptides (ADEPs) represent an attractive class of antimicrobial agents that act through dysregulation of caseinolytic protease (ClpP). Previous studies have shown that ADEPs are active against Gram-positive bacteria (e.g., MRSA, VRE, PRSP (penicillin-resistant Streptococcus pneumoniae)); however, there are currently few studies examining Gram-negative bacteria. In this study, the synthesis and biological evaluation of 14 novel ADEPs against a variety of pathogenic Gram-negative and Gram-positive organisms is outlined. Optimization of the macrocyclic core residues and N-acyl side chain culminated in the development of 26, which shows potent activity against the Gram-negative species Neisseria meningitidis and Neisseria gonorrheae and improved activity against the Gram-positive organisms Staphylococcus aureus and Enterococcus faecalis in comparison with known analogues. In addition, the co-crystal structure of an ADEP-ClpP complex derived from N. meningitidis was solved. | |||
Development and Characterization of Potent Cyclic Acyldepsipeptide Analogues with Increased Antimicrobial Activity.,Goodreid JD, Janetzko J, Santa Maria JP Jr, Wong KS, Leung E, Eger BT, Bryson S, Pai EF, Gray-Owen SD, Walker S, Houry WA, Batey RA J Med Chem. 2016 Jan 28;59(2):624-46. doi: 10.1021/acs.jmedchem.5b01451. Epub, 2016 Jan 12. PMID:26818454<ref>PMID:26818454</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5dkp" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Clp protease 3D structures|Clp protease 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Batey | [[Category: Neisseria meningitidis MC58]] | ||
[[Category: Bryson | [[Category: Synthetic construct]] | ||
[[Category: Eger | [[Category: Batey RA]] | ||
[[Category: Goodreid | [[Category: Bryson S]] | ||
[[Category: Gray-Owen | [[Category: Eger BT]] | ||
[[Category: Houry | [[Category: Goodreid JD]] | ||
[[Category: Janetzko | [[Category: Gray-Owen SD]] | ||
[[Category: Leung | [[Category: Houry WA]] | ||
[[Category: | [[Category: Janetzko J]] | ||
[[Category: | [[Category: Leung E]] | ||
[[Category: Walker | [[Category: Pai EF]] | ||
[[Category: Wong | [[Category: Santa Maria Jr JP]] | ||
[[Category: Walker S]] | |||
[[Category: Wong K]] | |||