2oid: Difference between revisions
New page: left|200px<br /> <applet load="2oid" size="450" color="white" frame="true" align="right" spinBox="true" caption="2oid, resolution 2.30Å" /> '''Crystal structure o... |
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[[Image:2oid.gif|left|200px]]<br /> | [[Image:2oid.gif|left|200px]]<br /><applet load="2oid" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2oid, resolution 2.30Å" /> | caption="2oid, resolution 2.30Å" /> | ||
'''Crystal structure of IRAK4 kinase domain complexed with AMPPNP'''<br /> | '''Crystal structure of IRAK4 kinase domain complexed with AMPPNP'''<br /> | ||
==Overview== | ==Overview== | ||
IL-1R-associated kinase (IRAK)4 plays a central role in innate and | IL-1R-associated kinase (IRAK)4 plays a central role in innate and adaptive immunity, and is a crucial component in IL-1/TLR signaling. We have determined the crystal structures of the apo and ligand-bound forms of human IRAK4 kinase domain. These structures reveal several features that provide opportunities for the design of selective IRAK4 inhibitors. The N-terminal lobe of the IRAK4 kinase domain is structurally distinctive due to a loop insertion after an extended N-terminal helix. The gatekeeper residue is a tyrosine, a unique feature of the IRAK family. The IRAK4 structures also provide insights into the regulation of its activity. In the apo structure, two conformations coexist, differing in the relative orientation of the two kinase lobes and the position of helix C. In the presence of an ATP analog only one conformation is observed, indicating that this is the active conformation. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
2OID 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 ANP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http:// | 2OID 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=ANP:'>ANP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OID OCA]. | ||
==Reference== | ==Reference== | ||
Cutting Edge: IL-1 | Cutting Edge: IL-1 receptor-associated kinase 4 structures reveal novel features and multiple conformations., Kuglstatter A, Villasenor AG, Shaw D, Lee SW, Tsing S, Niu L, Song KW, Barnett JW, Browner MF, J Immunol. 2007 Mar 1;178(5):2641-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17312103 17312103] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Browner, M | [[Category: Browner, M F.]] | ||
[[Category: Kuglstatter, A.]] | [[Category: Kuglstatter, A.]] | ||
[[Category: Villasenor, A | [[Category: Villasenor, A G.]] | ||
[[Category: ANP]] | [[Category: ANP]] | ||
[[Category: kinase]] | [[Category: kinase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:18:50 2008'' | ||
Revision as of 19:18, 21 February 2008
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Crystal structure of IRAK4 kinase domain complexed with AMPPNP
OverviewOverview
IL-1R-associated kinase (IRAK)4 plays a central role in innate and adaptive immunity, and is a crucial component in IL-1/TLR signaling. We have determined the crystal structures of the apo and ligand-bound forms of human IRAK4 kinase domain. These structures reveal several features that provide opportunities for the design of selective IRAK4 inhibitors. The N-terminal lobe of the IRAK4 kinase domain is structurally distinctive due to a loop insertion after an extended N-terminal helix. The gatekeeper residue is a tyrosine, a unique feature of the IRAK family. The IRAK4 structures also provide insights into the regulation of its activity. In the apo structure, two conformations coexist, differing in the relative orientation of the two kinase lobes and the position of helix C. In the presence of an ATP analog only one conformation is observed, indicating that this is the active conformation.
DiseaseDisease
Known diseases associated with this structure: IRAK4 deficiency OMIM:[606883], Invasive pneumococcal disease, recurrent isolated, 1 OMIM:[606883]
About this StructureAbout this Structure
2OID is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
ReferenceReference
Cutting Edge: IL-1 receptor-associated kinase 4 structures reveal novel features and multiple conformations., Kuglstatter A, Villasenor AG, Shaw D, Lee SW, Tsing S, Niu L, Song KW, Barnett JW, Browner MF, J Immunol. 2007 Mar 1;178(5):2641-5. PMID:17312103
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