This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2ozo
From Proteopedia
(New page: 200px<br /> <applet load="2ozo" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ozo, resolution 2.600Å" /> '''Autoinhibited inta...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2ozo. | + | [[Image:2ozo.jpg|left|200px]]<br /><applet load="2ozo" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2ozo" size=" | + | |
caption="2ozo, resolution 2.600Å" /> | caption="2ozo, resolution 2.600Å" /> | ||
'''Autoinhibited intact human ZAP-70'''<br /> | '''Autoinhibited intact human ZAP-70'''<br /> | ||
| Line 6: | Line 5: | ||
==Overview== | ==Overview== | ||
ZAP-70, a cytoplasmic tyrosine kinase required for T cell antigen receptor, signaling, is controlled by a regulatory segment that includes a tandem, SH2 unit responsible for binding to immunoreceptor tyrosine-based, activation motifs (ITAMs). The crystal structure of autoinhibited ZAP-70, reveals that the inactive kinase domain adopts a conformation similar to, that of cyclin-dependent kinases and Src kinases. The autoinhibitory, mechanism of ZAP-70 is, however, distinct and involves interactions, between the regulatory segment and the hinge region of the kinase domain, that reduce its flexibility. Two tyrosine residues in the SH2-kinase, linker that activate ZAP-70 when phosphorylated are involved in, aromatic-aromatic interactions that connect the linker to the kinase, domain. These interactions are inconsistent with ITAM binding, suggesting, that destabilization of this autoinhibited ZAP-70 conformation is the, first step in kinase activation. | ZAP-70, a cytoplasmic tyrosine kinase required for T cell antigen receptor, signaling, is controlled by a regulatory segment that includes a tandem, SH2 unit responsible for binding to immunoreceptor tyrosine-based, activation motifs (ITAMs). The crystal structure of autoinhibited ZAP-70, reveals that the inactive kinase domain adopts a conformation similar to, that of cyclin-dependent kinases and Src kinases. The autoinhibitory, mechanism of ZAP-70 is, however, distinct and involves interactions, between the regulatory segment and the hinge region of the kinase domain, that reduce its flexibility. Two tyrosine residues in the SH2-kinase, linker that activate ZAP-70 when phosphorylated are involved in, aromatic-aromatic interactions that connect the linker to the kinase, domain. These interactions are inconsistent with ITAM binding, suggesting, that destabilization of this autoinhibited ZAP-70 conformation is the, first step in kinase activation. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Selective T-cell defect OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176947 176947]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2OZO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and ANP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] Full crystallographic information is available from [http:// | + | 2OZO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=ANP:'>ANP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OZO OCA]. |
==Reference== | ==Reference== | ||
| Line 33: | Line 29: | ||
[[Category: tcr signaling]] | [[Category: tcr signaling]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:59:18 2008'' |
Revision as of 12:59, 23 January 2008
|
Autoinhibited intact human ZAP-70
Overview
ZAP-70, a cytoplasmic tyrosine kinase required for T cell antigen receptor, signaling, is controlled by a regulatory segment that includes a tandem, SH2 unit responsible for binding to immunoreceptor tyrosine-based, activation motifs (ITAMs). The crystal structure of autoinhibited ZAP-70, reveals that the inactive kinase domain adopts a conformation similar to, that of cyclin-dependent kinases and Src kinases. The autoinhibitory, mechanism of ZAP-70 is, however, distinct and involves interactions, between the regulatory segment and the hinge region of the kinase domain, that reduce its flexibility. Two tyrosine residues in the SH2-kinase, linker that activate ZAP-70 when phosphorylated are involved in, aromatic-aromatic interactions that connect the linker to the kinase, domain. These interactions are inconsistent with ITAM binding, suggesting, that destabilization of this autoinhibited ZAP-70 conformation is the, first step in kinase activation.
About this Structure
2OZO is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Non-specific protein-tyrosine kinase, with EC number 2.7.10.2 Full crystallographic information is available from OCA.
Reference
Structural basis for the inhibition of tyrosine kinase activity of ZAP-70., Deindl S, Kadlecek TA, Brdicka T, Cao X, Weiss A, Kuriyan J, Cell. 2007 May 18;129(4):735-46. PMID:17512407
Page seeded by OCA on Wed Jan 23 14:59:18 2008
