4H1D

Cocrystal structure of GlpG and DFP

Summary for 4H1D

• Entry DOI: 10.2210/pdb4h1d/pdb
• Descriptor: Rhomboid protease GlpG, DIISOPROPYL PHOSPHONATE (3 entities in total)
• Functional Keywords: intramembrane protease, serine protease, dfp, membrane protein, hydrolase
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane; Multi-pass membrane protein: P09391
• Total number of polymer chains: 1
• Total formula weight: 20380.17

Authors

Xue, Y.,Ha, Y. (deposition date: 2012-09-10, release date: 2013-05-01, Last modification date: 2024-11-20)

Primary citation

Xue, Y.,Ha, Y.
Large lateral movement of transmembrane helix s5 is not required for substrate access to the active site of rhomboid intramembrane protease.
J.Biol.Chem., 288:16645-16654, 2013

PubMed Abstract: Rhomboids represent an evolutionarily ancient protease family. Unlike most other proteases, they are polytopic membrane proteins and specialize in cleaving transmembrane protein substrates. The polar active site of rhomboid protease is embedded in the membrane and normally closed. For the bacterial rhomboid GlpG, it has been proposed that one of the transmembrane helices (S5) of the protease can rotate to open a lateral gate, enabling substrate to enter the protease from inside the membrane. Here, we studied the conformational change in GlpG by solving the cocrystal structure of the protease with a mechanism-based inhibitor. We also examined the lateral gating model by cross-linking S5 to a neighboring helix (S2). The crystal structure shows that inhibitor binding displaces a capping loop (L5) from the active site but causes only minor shifts in the transmembrane helices. Cross-linking S5 and S2, which not only restricts the lateral movement of S5 but also prevents substrate from passing between the two helices, does not hinder the ability of the protease to cleave a membrane protein substrate in detergent solution and in reconstituted membrane vesicles. Taken together, these data suggest that a large lateral movement of the S5 helix is not required for substrate access to the active site of rhomboid protease.

PubMed: 23609444
DOI: 10.1074/jbc.M112.438127

Experimental method

X-RAY DIFFRACTION (2.8975 Å)