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...) |
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| - | [[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 /> | ||
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==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. | ||
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| - | ==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== | ||
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[[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
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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
