5DKP: Crystal Structure Of N. Meningitidis Clpp In Complex With Agonist Adep A54556

Citation:
Abstract
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.
PDB ID: 5DKPDownload
MMDB ID: 136030
PDB Deposition Date: 2015/9/3
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.38  Å
Source Organism:
Neisseria meningitidis MC58
Similar Structures:
Biological Unit for 5DKP: 28-meric; determined by author
Molecular Components in 5DKP
Label Count Molecule
Proteins (28 molecules)
14
Atp-dependent CLP Protease Proteolytic Subunit(Gene symbol: clpP)
Molecule annotation
14
Agonist Adep A54556
Molecule annotation
Chemicals (14 molecules)
1
14
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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