ArticleBiochemistry2012
Conformational change in rhomboid protease GlpG induced by inhibitor binding to its S' subsites.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 53 citations in OpenAlex.
- Targeting the Membrane-Embedded Rhomboid Protease GlpG: A Multimodal Strategy for Inhibitor Discovery and Mechanistic Insight.Angewandte Chemie (International ed. in English) · 2026Article
- Effect of Environmental Factors on the Catalytic Activity of Intramembrane Serine Protease.Journal of the American Chemical Society · 2022Article
- A combination of solid-state NMR and MD simulations reveals the binding mode of a rhomboid protease inhibitor.Chemical science · 2021Article
- Rapid synthesis of internal peptidyl α-ketoamides by on resin oxidation for the construction of rhomboid protease inhibitors.RSC advances · 2021Article
- Late-Stage Conversion of Diphenylphosphonate to Fluorophosphonate Probes for the Investigation of Serine Hydrolases.Cell chemical biology · 2019Article
- Unwinding of the Substrate Transmembrane Helix in Intramembrane Proteolysis.Biophysical journal · 2018Article
- Discovery and Biological Evaluation of Potent and Selective N-Methylene Saccharin-Derived Inhibitors for Rhomboid Intramembrane Proteases.Biochemistry · 2017Article
- General and Modular Strategy for Designing Potent, Selective, and Pharmacologically Compliant Inhibitors of Rhomboid Proteases.Cell chemical biology · 2017Article
- The β-isoform of BCCIP promotes ADP release from the RAD51 presynaptic filament and enhances homologous DNA pairing.Nucleic acids research · 2017Article
- Reversible Unfolding of Rhomboid Intramembrane Proteases.Biophysical journal · 2016Article
- Crystal Structures and Inhibition Kinetics Reveal a Two-Stage Catalytic Mechanism with Drug Design Implications for Rhomboid Proteolysis.Molecular cell · 2016Article
- Membrane Protein Structure, Function, and Dynamics: a Perspective from Experiments and Theory.The Journal of membrane biology · 2015Review
- Substrate binding and specificity of rhomboid intramembrane protease revealed by substrate-peptide complex structures.The EMBO journal · 2014Article
- Stress-triggered activation of the metalloprotease Oma1 involves its C-terminal region and is important for mitochondrial stress protection in yeast.The Journal of biological chemistry · 2014Article
- Proteolysis inside the membrane is a rate-governed reaction not driven by substrate affinity.Cell · 2013Article
- Bioinformatics perspective on rhomboid intramembrane protease evolution and function.Biochimica et biophysica acta · 2013Review
- Biochemical and structural insights into intramembrane metalloprotease mechanisms.Biochimica et biophysica acta · 2013Review
- Residues in conserved loops of intramembrane metalloprotease SpoIVFB interact with residues near the cleavage site in pro-σK.Journal of bacteriology · 2013Article
- Large lateral movement of transmembrane helix S5 is not required for substrate access to the active site of rhomboid intramembrane protease.The Journal of biological chemistry · 2013Article
- Structure of rhomboid protease in complex with β-lactam inhibitors defines the S2' cavity.Structure (London, England : 1993) · 2013Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Rhomboid protease conducts proteolysis inside the hydrophobic environment of the membrane. The conformational flexibility of the protease is essential for the enzyme mechanism, but the nature of this flexibility is not completely understood. Here we describe the crystal structure of rhomboid protease GlpG in complex with a phosphonofluoridate inhibitor, which is covalently bonded to the catalytic serine and extends into the S' side of the substrate binding cleft. Inhibitor binding causes subtle but extensive changes in the membrane protease. Many transmembrane helices tilt and shift positions, and the gap between S2 and S5 is slightly widened so that the inhibitor can bind between them. The side chain of Phe-245 from a loop (L5) that acts as a cap rotates and uncovers the opening of the substrate binding cleft to the lipid bilayer. A concurrent turn of the polypeptide backbone at Phe-245 moves the rest of the cap and exposes the catalytic serine to the aqueous solution. This study, together with earlier crystallographic investigation of smaller inhibitors, suggests a simple model for explaining substrate binding to rhomboid protease.
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Registered trials
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