5DKP

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

5DKP の概要

• エントリーDOI: 10.2210/pdb5dkp/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000503
• 分子名称: ATP-dependent Clp protease proteolytic subunit, agonist ADEP A54556, POTASSIUM ION, ... (5 entities in total)
• 機能のキーワード: hydrolase, agonist, degradation, antimicrobial, hydrolase-antibiotic complex, hydrolase/antibiotic
• 由来する生物種: Neisseria meningitidis serogroup B (strain MC58); 詳細
• タンパク質・核酸の鎖数: 56
• 化学式量合計: 663700.30

構造登録者

Goodreid, J.D.,Janetzko, J.,Santa Maria Jr., J.P.,Wong, K.,Leung, E.,Eger, B.T.,Bryson, S.,Pai, E.F.,Gray-Owen, S.D.,Walker, S.,Houry, W.A.,Batey, R.A. (登録日: 2015-09-03, 公開日: 2016-01-27, 最終更新日: 2023-11-15)

主引用文献

Goodreid, J.D.,Janetzko, J.,Santa Maria, J.P.,Wong, K.S.,Leung, E.,Eger, B.T.,Bryson, S.,Pai, E.F.,Gray-Owen, S.D.,Walker, S.,Houry, W.A.,Batey, R.A.
Development and Characterization of Potent Cyclic Acyldepsipeptide Analogues with Increased Antimicrobial Activity.
J.Med.Chem., 59:624-646, 2016

PubMed 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.

PubMed: 26818454
DOI: 10.1021/acs.jmedchem.5b01451

実験手法

X-RAY DIFFRACTION (2.381 Å)