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Literature summary for 2.7.11.25 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
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Activating Compound

Activating Compound Comment Organism Structure
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)

Crystallization (Comment) Organism
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

Inhibitors Comment Organism Structure
14-3-3 the binding site is on the CR2 domain of the enzyme Homo sapiens
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

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

Natural Substrates/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

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

Synonyms

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

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens

General Information

General Information Comment Organism
evolution the enzyme belongs to the RAF (rapidly accelerated fibrosarcoma) kinase family Homo sapiens
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
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
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