2ozo: Difference between revisions

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|PDB= 2ozo |SIZE=350|CAPTION= <scene name='initialview01'>2ozo</scene>, resolution 2.600&Aring;
|PDB= 2ozo |SIZE=350|CAPTION= <scene name='initialview01'>2ozo</scene>, resolution 2.600&Aring;
|SITE=  
|SITE=  
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER'>ANP</scene>
|LIGAND= <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
|ACTIVITY= [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]  
|ACTIVITY= <span class='plainlinks'>[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] </span>
|GENE= ZAP70, SRK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
|GENE= ZAP70, SRK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
|DOMAIN=
|RELATEDENTRY=
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ozo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ozo OCA], [http://www.ebi.ac.uk/pdbsum/2ozo PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ozo RCSB]</span>
}}
}}


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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.
==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==
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[[Category: Kuriyan, J.]]
[[Category: Kuriyan, J.]]
[[Category: Weiss, A.]]
[[Category: Weiss, A.]]
[[Category: ANP]]
[[Category: MG]]
[[Category: autoinhibition]]
[[Category: autoinhibition]]
[[Category: hydrogen bonding network]]
[[Category: hydrogen bonding network]]
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[[Category: tcr signaling]]
[[Category: tcr signaling]]


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