Enzyme inhibitor discovery by activity-based protein profiling

MJ Niphakis, BF Cravatt - Annual review of biochemistry, 2014 - annualreviews.org
Eukaryotic and prokaryotic organisms possess huge numbers of uncharacterized enzymes.
Selective inhibitors offer powerful probes for assigning functions to enzymes in native …

Clp chaperones and proteases are central in stress survival, virulence and antibiotic resistance of Staphylococcus aureus

D Frees, U Gerth, H Ingmer - International Journal of Medical Microbiology, 2014 - Elsevier
Intracellular proteolysis carried out by energy-dependent proteases is one of the most
conserved biological processes. In all cells proteolysis maintains and shapes the cellular …

A processive rotary mechanism couples substrate unfolding and proteolysis in the ClpXP degradation machinery

ZA Ripstein, S Vahidi, WA Houry, JL Rubinstein… - Elife, 2020 - elifesciences.org
The ClpXP degradation machine consists of a hexameric AAA+ unfoldase (ClpX) and a pair
of heptameric serine protease rings (ClpP) that unfold, translocate, and subsequently …

AAA+ chaperones and acyldepsipeptides activate the ClpP protease via conformational control

M Gersch, K Famulla, M Dahmen, C Göbl… - Nature …, 2015 - nature.com
The Clp protease complex degrades a multitude of substrates, which are engaged by a
AAA+ chaperone such as ClpX and subsequently digested by the dynamic, barrel-shaped …

Cryo-EM structure of the ClpXP protein degradation machinery

C Gatsogiannis, D Balogh, F Merino… - Nature structural & …, 2019 - nature.com
The ClpXP machinery is a two-component protease complex that performs targeted protein
degradation in bacteria and mitochondria. The complex consists of the AAA+ chaperone …

Phenyl esters are potent inhibitors of caseinolytic protease P and reveal a stereogenic switch for deoligomerization

MW Hackl, M Lakemeyer, M Dahmen… - Journal of the …, 2015 - ACS Publications
Caseinolytic protease P (ClpP) represents a central bacterial degradation machinery that is
involved in cell homeostasis and pathogenicity. The functional role of ClpP has been studied …

Conformational control of the bacterial Clp protease by natural product antibiotics

IT Malik, H Brötz-Oesterhelt - Natural product reports, 2017 - pubs.rsc.org
Covering: up to 2017 The bacterial Clp protease is a highly conserved and structurally
versatile machine. It has gained a lot of recognition during the last decade as a novel …

Quercetin reduces the virulence of S. aureus by targeting ClpP to protect mice from MRSA-induced lethal pneumonia

S Jing, X Kong, L Wang, H Wang, J Feng… - Microbiology …, 2022 - Am Soc Microbiol
The dramatic increase of methicillin-resistant Staphylococcus aureus (MRSA) poses a great
challenge to the treatment of Staphylococcus aureus (S. aureus) infections. Therefore, there …

An allosteric switch regulates Mycobacterium tuberculosis ClpP1P2 protease function as established by cryo-EM and methyl-TROSY NMR

S Vahidi, ZA Ripstein, JB Juravsky… - Proceedings of the …, 2020 - National Acad Sciences
The 300-kDa ClpP1P2 protease from Mycobacterium tuberculosis collaborates with the
AAA+ (ATPases associated with a variety of cellular activities) unfoldases, ClpC1 and ClpX …

Mechanism of the allosteric activation of the ClpP protease machinery by substrates and active-site inhibitors

J Felix, K Weinhäupl, C Chipot, F Dehez, A Hessel… - Science …, 2019 - science.org
Coordinated conformational transitions in oligomeric enzymatic complexes modulate
function in response to substrates and play a crucial role in enzyme inhibition and activation …