Cloned (Comment) | Organism |
---|---|
recombinant expression of N-terminally His6-tagged enzyme in Spodooptera frugiperda Sf9 cells | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
purified recombinant detagged enzyme in complex with inhibitors 6-benzyl-3-[(2R)-2-(3-fluoropyridin-2-yl)-6-methyl-3,4-dihydro-2H-1-benzopyran-7-yl]-4,6-dihydropyrido[4,3-d]pyrimidine-2,7(1H,3H)-dione, 6-benzyl-3-[3-(benzyloxy)phenyl]-4,6-dihydropyrido[4,3-d]pyrimidine-2,7(1H,3H)-dione, and 3-[5-[(Z)-(2-cyclohexyl-5-imino-7-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-6(7H)-ylidene)methyl]furan-2-yl]benzoic acid, X-ray diffraction structure determination and analysis at 2.75 A, 2.95 A, and 2.80 A resolution, respectivly | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(6Z)-6-[[5-(3-chlorophenyl)furan-2-yl]methylidene]-5-imino-2-propyl-5,6-dihydro-7H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-one | - |
Homo sapiens | |
3-[5-[(Z)-(2-cyclohexyl-5-imino-7-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-6(7H)-ylidene)methyl]furan-2-yl]benzoic acid | binds an RNA-binding site inside the N-terminal cassette, mechanism of action, enzyme binding structure, overview | Homo sapiens | |
3-[5-[(Z)-(5-imino-7-oxo-2-propyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-6(7H)-ylidene)methyl]furan-2-yl]benzoic acid | - |
Homo sapiens | |
6-benzyl-3-[(2R)-2-(3-fluoropyridin-2-yl)-6-methyl-3,4-dihydro-2H-1-benzopyran-7-yl]-4,6-dihydropyrido[4,3-d]pyrimidine-2,7(1H,3H)-dione | binds to an unexpected allosteric site between the C-terminal and the N-terminal helicase cassettes, enzyme binding structure, overview | Homo sapiens | |
6-benzyl-3-[3-(benzyloxy)phenyl]-4,6-dihydropyrido[4,3-d]pyrimidine-2,7(1H,3H)-dione | enzyme binding structure, overview | Homo sapiens | |
additional information | selectivity profiling indicated the allosteric inhibitor 6-benzyl-3-[(2R)-2-(3-fluoropyridin-2-yl)-6-methyl-3,4-dihydro-2H-1-benzopyran-7-yl]-4,6-dihydropyrido[4,3-d]pyrimidine-2,7(1H,3H)-dione is more Brr2-selective than the RNA site binder 3-[5-[(Z)-(2-cyclohexyl-5-imino-7-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-6(7H)-ylidene)methyl]furan-2-yl]benzoic acid | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + H2O | Homo sapiens | - |
ADP + phosphate | - |
? | |
additional information | Homo sapiens | enzyme Brr2 catalyzes an ATP-dependent unwinding of the U4/U6 RNA duplex | ? | - |
- |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | O75643 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant His6-tagged enzyme from Spodoptera frugiperda Sf9 cells by nickel affinity chromatography, tag cleavage by TEV protease, follwed by dialysis, another step of nickel affinity chromatography, and ultrafiltration of the flow-through | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + H2O | - |
Homo sapiens | ADP + phosphate | - |
? | |
additional information | enzyme Brr2 catalyzes an ATP-dependent unwinding of the U4/U6 RNA duplex | Homo sapiens | ? | - |
- |
Synonyms | Comment | Organism |
---|---|---|
BRR2 | - |
Homo sapiens |
spliceosomal RNA helicase | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0042 | - |
pH and temperature not specified in the publication | Homo sapiens | 3-[5-[(Z)-(5-imino-7-oxo-2-propyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-6(7H)-ylidene)methyl]furan-2-yl]benzoic acid | |
0.0053 | - |
pH and temperature not specified in the publication | Homo sapiens | 3-[5-[(Z)-(2-cyclohexyl-5-imino-7-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-6(7H)-ylidene)methyl]furan-2-yl]benzoic acid | |
0.1 | - |
above, pH and temperature not specified in the publication | Homo sapiens | (6Z)-6-[[5-(3-chlorophenyl)furan-2-yl]methylidene]-5-imino-2-propyl-5,6-dihydro-7H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-one |
General Information | Comment | Organism |
---|---|---|
evolution | Brr2 is an RNA helicase belonging to the Ski2-like subfamily | Homo sapiens |
physiological function | Brr2 is an essential component of spliceosome. Brr2 catalyzes an ATP-dependent unwinding of the U4/U6 RNA duplex, which is a critical step for spliceosomal activation | Homo sapiens |