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Literature summary extracted from

  • Aramini, J.; Vorobiev, S.; Tuberty, L.; Janjua, H.; Campbell, E.; Seetharaman, J.; Su, M.; Huang, Y.; Acton, T.; Xiao, R.; Tong, L.; Montelione, G.
    The RAS-binding domain of human BRAF protein serine/threonine kinase exhibits allosteric conformational changes upon binding HRAS (2015), Structure, 23, 1382-1393 .
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.11.25 Ras the interaction of the two oncoproteins RAS and BRAF is absolutely required for activation of the MAPK pathway, binding structure analysis, detailed overview. Allosteric conformational changes upon RAS binding, propagated through the beta-sheet and alpha-helical core of the protein domain.Changes in BRAF RAS-binding domain (RBD) that accompany RAS binding provide a basis for allosteric regulation of BRAF structure and function, and suggest a mechanism by which RAS binding can signal domain rearrangements required for activation of BRAF kinase Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.11.25 purified recombinant RAS-binding domain (RBD) from human B-RAF kinase, by microbatch-under-oil crystallization method at 18°C, X-ray diffraction structure determination and analysis at 2.0 A resolution Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.11.25 14-3-3 the binding site is on the CR2 domain of the enzyme Homo sapiens
2.7.11.25 additional information RAF kinases are inhibited by autoinhibitory domains, which precludes dimerization of the kinase domain and renders the enzyme inactive Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.11.25 Mg2+ required Homo sapiens
2.7.11.25 Zn2+ 2 Zn2+ are bound at region CR1 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.11.25 ATP + Mek1 Homo sapiens activation ADP + phospho-Mek1
-
 ?
2.7.11.25 ATP + MEK2 Homo sapiens activation ADP + phospho-MEK2
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.11.25 Homo sapiens
-
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.11.25 ATP + Mek1 activation Homo sapiens ADP + phospho-Mek1
-
 ?
2.7.11.25 ATP + MEK2 activation Homo sapiens ADP + phospho-MEK2
-
 ?
2.7.11.25 additional information RAF kinases exhibit high substrate selectivity, exclusively targeting the dual-specificity (Tyr/Thr) kinases MEK1/2 Homo sapiens ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.11.25 BRAF
-
 Homo sapiens
2.7.11.25 BRAF protein serine/threonine kinase
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.11.25 ATP
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
2.7.11.25 evolution the enzyme belongs to the RAF (rapidly accelerated fibrosarcoma) kinase family Homo sapiens
2.7.11.25 metabolism the interaction of the two oncoproteins RAS and BRAF is absolutely required for activation of the MAPK pathway, binding structure analysis, overview Homo sapiens
2.7.11.25 additional information NMR structure analysis of RAS-binding domain (RBD) from human B-RAF kinase, and analysis of the complex between B-RAF RBD and the GppNHp bound form of HRAS in solution, overview. B-Raf CR1 region is composed of a RAS-binding domain (RBD) immediately followed by a cysteine-rich domain, which can bind two zinc ions. CR1 interacts with RAS and membrane phospholipids. Region CR2 is a serine/threonine-rich domain containing a 14-3-3 binding site, and region CR3 features the kinase domain. RAS and BRAF binding structure analysis, detailed overview. Allosteric conformational changes upon RAS binding, propagated through the beta-sheet and alpha-helical core of the protein domain Homo sapiens
2.7.11.25 physiological function RAF kinases exhibit high substrate selectivity, exclusively targeting the dual-specificity (Tyr/Thr) kinases MEK1/2. Regulation of RAF kinases is extremely complex and strictly controlled by several factors and events, including protein-protein interactions, phosphorylation/dephosphorylation at numerous sites, and oligomerization state Homo sapiens