2cn5: Difference between revisions

Line 4:

==Overview==

The protein kinase Chk2 (checkpoint kinase 2) is a major effector of the, replication checkpoint. Chk2 activation is initiated by phosphorylation of, Thr68, in the serine-glutamine/threonine-glutamine cluster domain (SCD), by ATM. The phosphorylated SCD-segment binds to the FHA domain of a second, Chk2 molecule, promoting dimerisation of the protein and triggering, phosphorylation of the activation segment/T-loop in the kinase domain. We, have now determined the structure of the kinase domain of human Chk2 in, complexes with ADP and a small-molecule inhibitor debromohymenialdisine., The structure reveals a remarkable dimeric arrangement in which T-loops, are exchanged between protomers, to form an active kinase conformation in, trans. Biochemical data suggest that this dimer is the biologically active, state promoted by ATM-phosphorylation, and also suggests a mechanism for, dimerisation-driven activation of Chk2 by trans-phosphorylation.

The protein kinase Chk2 (checkpoint kinase 2) is a major effector of the replication checkpoint. Chk2 activation is initiated by phosphorylation of Thr68, in the serine-glutamine/threonine-glutamine cluster domain (SCD), by ATM. The phosphorylated SCD-segment binds to the FHA domain of a second Chk2 molecule, promoting dimerisation of the protein and triggering phosphorylation of the activation segment/T-loop in the kinase domain. We have now determined the structure of the kinase domain of human Chk2 in complexes with ADP and a small-molecule inhibitor debromohymenialdisine. The structure reveals a remarkable dimeric arrangement in which T-loops are exchanged between protomers, to form an active kinase conformation in trans. Biochemical data suggest that this dimer is the biologically active state promoted by ATM-phosphorylation, and also suggests a mechanism for dimerisation-driven activation of Chk2 by trans-phosphorylation.

==Disease==

Line 17:

[[Category: Non-specific serine/threonine protein kinase]]

[[Category: Single protein]]

[[Category: Oliver, A.W.]]

[[Category: Oliver, A W.]]

[[Category: Pearl, L.H.]]

[[Category: Pearl, L H.]]

[[Category: ADP]]

[[Category: CL]]

Line 47:

[[Category: tumour suppressor]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun~~ Feb ~~3 10~~:37:10 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:50:23 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 4: / Line 4: @@
 ==Overview==
-The protein kinase Chk2 (checkpoint kinase 2) is a major effector of the, replication checkpoint. Chk2 activation is initiated by phosphorylation of, Thr68, in the serine-glutamine/threonine-glutamine cluster domain (SCD), by ATM. The phosphorylated SCD-segment binds to the FHA domain of a second, Chk2 molecule, promoting dimerisation of the protein and triggering, phosphorylation of the activation segment/T-loop in the kinase domain. We, have now determined the structure of the kinase domain of human Chk2 in, complexes with ADP and a small-molecule inhibitor debromohymenialdisine., The structure reveals a remarkable dimeric arrangement in which T-loops, are exchanged between protomers, to form an active kinase conformation in, trans. Biochemical data suggest that this dimer is the biologically active, state promoted by ATM-phosphorylation, and also suggests a mechanism for, dimerisation-driven activation of Chk2 by trans-phosphorylation.
+The protein kinase Chk2 (checkpoint kinase 2) is a major effector of the replication checkpoint. Chk2 activation is initiated by phosphorylation of Thr68, in the serine-glutamine/threonine-glutamine cluster domain (SCD), by ATM. The phosphorylated SCD-segment binds to the FHA domain of a second Chk2 molecule, promoting dimerisation of the protein and triggering phosphorylation of the activation segment/T-loop in the kinase domain. We have now determined the structure of the kinase domain of human Chk2 in complexes with ADP and a small-molecule inhibitor debromohymenialdisine. The structure reveals a remarkable dimeric arrangement in which T-loops are exchanged between protomers, to form an active kinase conformation in trans. Biochemical data suggest that this dimer is the biologically active state promoted by ATM-phosphorylation, and also suggests a mechanism for dimerisation-driven activation of Chk2 by trans-phosphorylation.
 ==Disease==
@@ Line 17: / Line 17: @@
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Single protein]]
-[[Category: Oliver, A.W.]]
+[[Category: Oliver, A W.]]
-[[Category: Pearl, L.H.]]
+[[Category: Pearl, L H.]]
 [[Category: ADP]]
 [[Category: CL]]
@@ Line 47: / Line 47: @@
 [[Category: tumour suppressor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:37:10 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:50:23 2008''