5dkp

Crystal Structure of N. meningitidis ClpP in complex with agonist ADEP A54556.

spinqualitylabelsall models 5dkp, resolution 2.38Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5dkp is a 56 chain structure with sequence from Neisseria meningitidis MC58 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.381Å Ligands: K, MAA, MP8, NA, OTT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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] 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Clp protease 3D structures

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