Sandbox Reserved 707: Difference between revisions

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'''The complex of wild type B-RAF and BAY439006'''

{{STRUCTURE_1uwh| PDB=1uwh | SCENE= |left}} [[Image:1uwh bio r 500.jpg|left|300px|thumb| The complex of wild type B-RAF and BAY439006 ([[1uwh]])]]

[[Image:1uwh bio r 500.jpg|left|300px|thumb| The complex of wild type B-RAF and BAY439006 ([[1uwh]])]]

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Although X-ray structures of B-RAF kinase domains were said to be monomeric, each of the six structures in the protein data bank (2009), including B-RAF (V600E), showed that the asymmetric unit of the crystal contains two kinase domains that interact in a unique side-to-side fashion involving the N-lobe. This side-to-side dimerization involves the αC helix, an important determinant of active and inactive conformations. Based upon ultracentrifugation studies, it is demonstrated that the catalytic domain of human B-RAF forms homodimers. Arg509 of B-RAF occurs in the side-to-side interface, and these investigators found that the Arg509 His mutant exists as a monomer. But B-RAF can form heterodimers too. Ser621 and residues in the αC helix of C-RAF participate in dimer formation. B-RAF–C-RAF heterodimers are more active than either homodimer. Phosphorylation of B-RAF at Thr753 as catalyzed by ERK destabilizes heterodimer formation with C-RAF and decreases kinase activity.

Although X-ray structures of B-RAF kinase domains were said to be monomeric, each of the six structures in the protein data bank (2009), including B-RAF (V600E), showed that the asymmetric unit of the crystal contains two kinase domains that interact in a unique side-to-side fashion involving the N-lobe. This side-to-side dimerization involves the αC helix, an important determinant of active and inactive conformations. Based upon ultracentrifugation studies, it is demonstrated that the catalytic domain of human B-RAF forms homodimers. Arg509 of B-RAF occurs in the side-to-side interface, and these investigators found that the Arg509 His mutant exists as a monomer. But B-RAF can form heterodimers too<ref>PMID:16508002</ref>. Ser621 and residues in the αC helix of C-RAF participate in dimer formation. B-RAF–C-RAF heterodimers are more active than either homodimer. Phosphorylation of B-RAF at Thr753 as catalyzed by ERK destabilizes heterodimer formation with C-RAF and decreases kinase activity.

Sandbox Reserved 707: Difference between revisions

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@@ Line 6: / Line 6: @@
 '''The complex of wild type B-RAF and BAY439006'''
-{{STRUCTURE_1uwh|  PDB=1uwh  |  SCENE=  |left}}
+{{STRUCTURE_1uwh|  PDB=1uwh  |  SCENE=  |left}} [[Image:1uwh bio r 500.jpg|left|300px|thumb| The complex of wild type B-RAF and BAY439006 ([[1uwh]])]]
-[[Image:1uwh bio r 500.jpg|left|300px|thumb| The complex of wild type B-RAF and BAY439006 ([[1uwh]])]]
@@ Line 95: / Line 94: @@
-Although X-ray structures of B-RAF kinase domains were said to be monomeric, each of the six structures in the protein data bank (2009), including B-RAF (V600E), showed that the asymmetric unit of the crystal contains two kinase domains that interact in a unique side-to-side fashion involving the N-lobe. This side-to-side dimerization involves the αC helix, an important determinant of active and inactive conformations. Based upon ultracentrifugation studies, it is demonstrated that the catalytic domain of human B-RAF forms homodimers. Arg509 of B-RAF occurs in the side-to-side interface, and these investigators found that the Arg509 His mutant exists as a monomer. But B-RAF can form heterodimers too. Ser621 and residues in the αC helix of C-RAF participate in dimer formation. B-RAF–C-RAF heterodimers are more active than either homodimer. Phosphorylation of B-RAF at Thr753 as catalyzed by ERK destabilizes heterodimer formation with C-RAF and decreases kinase activity.
+Although X-ray structures of B-RAF kinase domains were said to be monomeric, each of the six structures in the protein data bank (2009), including B-RAF (V600E), showed that the asymmetric unit of the crystal contains two kinase domains that interact in a unique side-to-side fashion involving the N-lobe. This side-to-side dimerization involves the αC helix, an important determinant of active and inactive conformations. Based upon ultracentrifugation studies, it is demonstrated that the catalytic domain of human B-RAF forms homodimers. Arg509 of B-RAF occurs in the side-to-side interface, and these investigators found that the Arg509 His mutant exists as a monomer. But B-RAF can form heterodimers too<ref>PMID:16508002</ref>. Ser621 and residues in the αC helix of C-RAF participate in dimer formation. B-RAF–C-RAF heterodimers are more active than either homodimer. Phosphorylation of B-RAF at Thr753 as catalyzed by ERK destabilizes heterodimer formation with C-RAF and decreases kinase activity.