Any feedback?
Please rate this page
(all_enzymes.php)
(0/150)

BRENDA support

3.4.21.105: rhomboid protease

This is an abbreviated version!
For detailed information about rhomboid protease, go to the full flat file.

Word Map on EC 3.4.21.105

Reaction

cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains =

Synonyms

AAR, AarA, AqRho, Derlin-1, EhROM1, GlpG, GlpP, intramembrane protease, microneme rhomboid protease, More, paGlpG, PARL, PBANKA_110650, PbROM1, Pcp1, Pcp1/Rbd1, pfROM4, presenilin associated rhomboid like protein, presenilin-associated rhomboid-like, presenilin-associated rhomboid-like protein, presenilins-associated rhomboid-like protein, PSARL, Rbd1, Rbd1p, RBL1, RBL10, RBL11, RBL12, RBL2, RBL3, RBL4, RBL5, RBL6, RBL7, RBL8, RBL9, Rhbdd1, RHBDL, RHBDL2, RHBDL4, RHDBL-2, Rho, RHO-1, rho-4, Rho-7, RhoII, Rhomboid, Rhomboid 4, rhomboid intramembrane protease, rhomboid Pcp1/Rbd1, rhomboid peptidase Pcp1, rhomboid protease, Rhomboid protease AarA, Rhomboid protease glpG, Rhomboid protease gluP, rhomboid protease Pcp1, rhomboid protease PSARL, Rhomboid protein, rhomboid protein 1, rhomboid protein 4, rhomboid pseudoprotease, rhomboid serine protease, rhomboid-1, rhomboid-1 protease, rhomboid-2, rhomboid-3, rhomboid-4, rhomboid-like protein, rhomboid-like protein 10, rhomboid-related protein 4, rhomboid-type protease Pcp1, ROM1, ROM4, ROM5, Spitz protease, TgROM1, TgROM2, TgROM3, TgROM4, TgROM5, Ygr101w, Yqgp

ECTree

     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.105 rhomboid protease

Crystallization

Crystallization on EC 3.4.21.105 - rhomboid protease

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
analysis of interaction energies among the active site residues His254, Ser201, and Asn154, which form a hydrogen bonding network. In mild detergent, the active site residues are weakly coupled with interaction energies of ?1.4 kcal/mol between His254 and Ser201 and ?0.2 kcal/mol between Ser201 and Asn154. These residues are important for function and also for the folding cooperativity of GlpG. The weak interaction between Ser and His in the catalytic dyad may partly explain the unusually slow proteolysis by GlpG
Coarse-grained molecular dynamics simulations in hydrated lipid bilayers to study the interaction of rhomboid protease GlpG with the transmembrane domain of the substrate Spitz. Spitz does not associate with GlpG exclusively at the putative substrate gate near TMD 5. Instead, there are six prominent and stable interaction sites, including one between TMDs 1 and 3, with the closest enzyme-substrate proximity occurring at the ends of helical transmembrane domains or in loops. The initial interaction between enzyme and substrate is not limited to a single site on the enzyme, and may be driven by juxtamembrane electrostatic interactions
-
crystal structure in complex with beta-lactam inhibitors phenyl 2-oxo-4-phenylazetidine-1-carboxylate, 2-methylpropyl 2-oxo-4-phenylazetidine-1-carboxylate, and cyclopentyl 2-oxo-4-phenylazetidine-1-carboxylate, to 2.2 to 2.4 A resolution
crystal structure of the soluble cytoplasmic domain, 1.35 Å resolution. The cytoplasmic domain exists as a dimer with extensive domain swapping between the two monomers. Domain-swapped dimers can be isolated from the full-length protein
crystals of the truncated GlpG wild type enzyme are obtained by mixing 2.5-3 M ammonium chloride with protein at ratio of 1:1 in hanging drops at 25°C
GlpG in a more open conformation, where the capping loop L5 has been lifted, exposing the previously buried and catalytically essential Ser201 to outside aqueous solution, X-ray diffraction structure determination and analysis at 2.5-2.6 A resolution
in complex with covalently bound inhibitor 3-butyl-4-(pent-4-yn-1-yl)oxetan-2-one
in complex with inhibitors 3,4-dichloroisocoumarin and diisopropyl fluorophosphonate, to 2.3 A resolution. Enzyme forms a covalent adduct with diisopropyl fluorophosphonate, which mimics the oxyanion-containing tetrahedral intermediate of the hydrolytic reaction. The oxyanion is stabilized by the main chain amide of residue Ser201 and by the side chains of His150 and Asn154. The phosphorylation of the catalytic Ser201 weakens its interaction with His254, causing the catalytic histidine to rotate away from the serine and accompanied by further rearrangement of the side chains of Tyr205 and Trp236 within the substrate-binding groove and by opening of the L5 cap and movement of transmembrane helix S5 toward S6 in a direction different from that predicted by the lateral gating model
in complex with inhibotrs acetyl-L-Ile-L-Ala-L-Thr-L-Ala-chloromethylketone, acetyl-L-Phe-L-Ala-L-Thr-L-Ala-chloromethylketone. Inhibitors bind in a substrate-like manner. The S1 subsite is prominent and merges into the water retention site, suggesting intimate interplay between substrate binding, specificity and catalysis. The S4 subsite is plastically formed by residues of the L1 loop, an important but hitherto enigmatic feature of the rhomboid fold
-
molecular dynamics simulation of substrate entry into the active site. Substrate is inclined to enter into the active site along a path between Loop3 and Loop5, and residue His150 plays an important role in substrate entry
molecular dynamics simulation. In both membrane and lipid-solubilized environments the S201/H254 and S201/H150 interatomic distances of GlpG are most sensitive to variations of the protonation state of the active site residues. The catalytic diad of the lipid-solubilized enzyme exists as an H254(+)-S201(-) ion pair at the Michaelis complex stage, with Ser201 ready for nucleophilic attack on the substrate. Therefore, deprotonation of S201 does not contribute to the activation barrier of covalent tetrahedral complex formation. Both catalytic residues, H254 and S201, are neutral in the Michaelis complex of GlpG in the membrane. Therefore, S201 deprotonation by H254 general base catalysis should contribute to the activation barrier of the covalent tetrahedral complex formation
molecular dynamics simulations initiated from both gate-open and gate-closed states of rhomboid GlpG in a phospholipid bilayer. There is rapid loss of crystallographic waters from the active site, but retention of a water cluster within a site formed by His141, Ser181, Ser185, and/or Gln189. Residues Gln189 and Ser185 play an essential role in catalysis with no effect on structural stability
purified GlpG core domain, hanging drop vapour diffusion method, room temperature, 5 mg/ml membrane protein in 10 mM Tris-HCl, pH 7.6, and 20 mM nonylglucoside, over a reservoir solution of 3 M NaCl and 100 mM Bis-Tris propane, pH 7.0, cryoprotection by 25% glycerol, 1 month, X-ray diffraction structure determination and analysis at 2.1 A resolution
purified recombinant His-tagged GlpG, hanging drop vapour diffusion method, 5 mg/ml protein in 20 mM HEPES, pH 7.5, 90 mM NaCl, 10% glycerol, and lauryl dimethylamine oxide, mixed with a reservoir solution containing 30% w/v PEG 400, 200 mM CaCl2, and 100 mM MES, pH 6.5, X-ray diffraction structure determination and analysis at 2.25-2.3 A resolution
rhomboid protease GlpG in complex with 3,4-dichloroisocoumarin and diisopropyl fluorophosphonate, sitting drop vapor diffusion method, using 100 mM Bis-Tris propane (pH 7.0), and 3 M NaCl
structure of Escherichia coli GlpG consists of a 6-transmembrane domain topology
structure of Escherichia coli GlpG consists of a 6-transmembrane domain topology. The active site of Escherichia coli GlpG is found at the bottom of a shallow pocket that faces the extracellular side of the membrane. Above the catalytic dyad is a loop structure which lies roughly parallel to the membrane plane. A side chain from the loop (Phe-245) drops down and seals a gap between two transmembrane helices. This loop structure sterically hinders substrate access to the catalytic serine and is intrinsically flexible
-
structure of Escherichia coli GlpG consists of a 6-transmembrane domain topology
-