3STA

Crystal structure of ClpP in tetradecameric form from Staphylococcus aureus

Summary for 3STA

• Entry DOI: 10.2210/pdb3sta/pdb
• Related: 3ST9
• Descriptor: ATP-dependent Clp protease proteolytic subunit (2 entities in total)
• Functional Keywords: atpase-dependent clp protease, hydrolase
• Biological source: staphylococcus aureus
• Cellular location: Cytoplasm (By similarity): P63786
• Total number of polymer chains: 14
• Total formula weight: 303529.27

Authors

Zhang, J.,Ye, F.,Lan, L.,Jiang, H.,Luo, C.,Yang, C.-G. (deposition date: 2011-07-09, release date: 2011-09-07, Last modification date: 2024-03-20)

Primary citation

Zhang, J.,Ye, F.,Lan, L.,Jiang, H.,Luo, C.,Yang, C.-G.
Structural switching of Staphylococcus aureus Clp protease: a key to understanding protease dynamics
J.Biol.Chem., 286:37590-37601, 2011

PubMed Abstract: ATP-dependent Clp protease (ClpP) is an attractive new target for the development of anti-infective agents. The ClpP protease consists of two heptameric rings that enclose a large chamber containing 14 proteolytic active sites. Recent studies indicate that ClpP likely undergoes conformational switching between an extended and degraded active state required for substrate proteolysis and a compacted and catalytically inactive state allowing product release. Here, we present the wild-type ClpP structures in two distinct states from Staphylococcus aureus. One structure is very similar to those solved ClpP structures in the extended states. The other is strikingly different from both the extended and the compacted state as observed in ClpP from other species; the handle domain of this structure kinks to take on a compressed conformation. Structural analysis and molecular dynamic simulations show that the handle domain predominantly controls the way in which degradation products exit the chamber through dynamic conformational switching from the extended state to the compressed state. Given the highly conserved sequences among ClpP from different species, this compressed conformation is unexpected and novel, which is potentially valuable for understanding the enzymatic dynamics and the acting mechanisms of ClpP.

PubMed: 21900233
DOI: 10.1074/jbc.M111.277848

Experimental method

X-RAY DIFFRACTION (2.28 Å)