2NR9

Crystal structure of GlpG, Rhomboid Peptidase from Haemophilus influenzae

Summary for 2NR9

• Entry DOI: 10.2210/pdb2nr9/pdb
• Related: 2IC8
• Descriptor: Protein glpG homolog, (R)-2-(FORMYLOXY)-3-(PHOSPHONOOXY)PROPYL PENTANOATE, 3,6,12,15,18,21,24-HEPTAOXAHEXATRIACONTAN-1-OL, ... (4 entities in total)
• Functional Keywords: intramembrane peptidase, rhomboid protease, membrane protein
• Biological source: Haemophilus influenzae
• Cellular location: Cell inner membrane; Multi-pass membrane protein: P44783
• Total number of polymer chains: 1
• Total formula weight: 24067.08

Authors

Lemieux, M.J.,Fischer, S.J.,Cherney, M.M.,Bateman, K.S.,James, M.N.G. (deposition date: 2006-11-01, release date: 2006-11-14, Last modification date: 2023-08-30)

Primary citation

Lemieux, M.J.,Fischer, S.J.,Cherney, M.M.,Bateman, K.S.,James, M.N.G.
The crystal structure of the rhomboid peptidase from Haemophilus influenzae provides insight into intramembrane proteolysis.
Proc.Natl.Acad.Sci.USA, 104:750-754, 2007

PubMed Abstract: Rhomboid peptidases are members of a family of regulated intramembrane peptidases that cleave the transmembrane segments of integral membrane proteins. Rhomboid peptidases have been shown to play a major role in developmental processes in Drosophila and in mitochondrial maintenance in yeast. Most recently, the function of rhomboid peptidases has been directly linked to apoptosis. We have solved the structure of the rhomboid peptidase from Haemophilus influenzae (hiGlpG) to 2.2-A resolution. The phasing for the crystals of hiGlpG was provided mainly by molecular replacement, by using the coordinates of the Escherichia coli rhomboid (ecGlpG). The structural results on these rhomboid peptidases have allowed us to speculate on the catalytic mechanism of substrate cleavage in a membranous environment. We have identified the relative disposition of the nucleophilic serine to the general base/acid function of the conserved histidine. Modeling a tetrapeptide substrate in the context of the rhomboid structure reveals an oxyanion hole comprising the side chain of a second conserved histidine and the main-chain NH of the nucleophilic serine residue. In both hiGlpG and ecGlpG structures, a water molecule occupies this oxyanion hole.

PubMed: 17210913
DOI: 10.1073/pnas.0609981104

Experimental method

X-RAY DIFFRACTION (2.2 Å)