3MT6

Structure of ClpP from Escherichia coli in complex with ADEP1

Summary for 3MT6

• Entry DOI: 10.2210/pdb3mt6/pdb
• Related: 1TYF 1Y7O 1YG6 2FZS 3KTG 3KTH 3KTI 3KTJ 3KTK
• Related PRD ID: PRD_000503
• Descriptor: ATP-dependent Clp protease proteolytic subunit, ACYLDEPSIPEPTIDE 1, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
• Functional Keywords: endopeptidase clp, caseinolytic protease, protease ti, acypdepsipeptide antibiotics, hydrolase-antibiotic complex, hydrolase/antibiotic
• Biological source: Escherichia coli; More
• Cellular location: Cytoplasm: P0A6G7
• Total number of polymer chains: 56
• Total formula weight: 677085.71

Authors

Chung, Y.S. (deposition date: 2010-04-30, release date: 2010-11-03, Last modification date: 2023-11-22)

Primary citation

Li, D.H.,Chung, Y.S.,Gloyd, M.,Joseph, E.,Ghirlando, R.,Wright, G.D.,Cheng, Y.Q.,Maurizi, M.R.,Guarne, A.,Ortega, J.
Acyldepsipeptide antibiotics induce the formation of a structured axial channel in ClpP: A model for the ClpX/ClpA-bound state of ClpP.
Chem.Biol., 17:959-969, 2010

PubMed Abstract: In ClpXP and ClpAP complexes, ClpA and ClpX use the energy of ATP hydrolysis to unfold proteins and translocate them into the self-compartmentalized ClpP protease. ClpP requires the ATPases to degrade folded or unfolded substrates, but binding of acyldepsipeptide antibiotics (ADEPs) to ClpP bypasses this requirement with unfolded proteins. We present the crystal structure of Escherichia coli ClpP bound to ADEP1 and report the structural changes underlying ClpP activation. ADEP1 binds in the hydrophobic groove that serves as the primary docking site for ClpP ATPases. Binding of ADEP1 locks the N-terminal loops of ClpP in a β-hairpin conformation, generating a stable pore through which extended polypeptides can be threaded. This structure serves as a model for ClpP in the holoenzyme ClpAP and ClpXP complexes and provides critical information to further develop this class of antibiotics.

PubMed: 20851345
DOI: 10.1016/j.chembiol.2010.07.008

Experimental method

X-RAY DIFFRACTION (1.901 Å)