1di8: Difference between revisions
New page: left|200px<br /> <applet load="1di8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1di8, resolution 2.20Å" /> '''THE STRUCTURE OF CY... |
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[[Image:1di8.gif|left|200px]]<br /> | [[Image:1di8.gif|left|200px]]<br /><applet load="1di8" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1di8, resolution 2.20Å" /> | caption="1di8, resolution 2.20Å" /> | ||
'''THE STRUCTURE OF CYCLIN-DEPENDENT KINASE 2 (CDK2) IN COMPLEX WITH 4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'''<br /> | '''THE STRUCTURE OF CYCLIN-DEPENDENT KINASE 2 (CDK2) IN COMPLEX WITH 4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'''<br /> | ||
==Overview== | ==Overview== | ||
4-Anilinoquinazolines represent an important class of protein kinase | 4-Anilinoquinazolines represent an important class of protein kinase inhibitor. Modes of binding for two members of this inhibitor class were determined by X-ray crystallographic analysis of one inhibitor (4-[3-hydroxyanilino]-6,7-dimethoxyquinazoline) in complex with cyclin-dependent kinase 2 (CDK2) and the other (4-[3-methylsulfanylanilino]-6,7-dimethoxyquinazoline) in complex with p38 kinase. In both inhibitor/kinase structures, the 4-anilinoquinazoline was bound in the ATP site with the quinazoline ring system oriented along the peptide strand that links the two domains of the protein and with the anilino substituent projecting into a hydrophobic pocket within the protein interior. In each case, the nitrogen at position-1 of the quinazoline accepted a hydrogen bond from a backbone NH (CDK2, Leu-83; p38, Met-109) of the domain connector strand, and aromatic hydrogen atoms at C2 and C8 interacted with backbone carbonyl oxygen atoms of the peptide strand. The anilino group of the CDK2-bound compound was essentially coplanar with the quinazoline ring system and occupied a pocket between Lys-33 and Phe-80. For the p38-bound inhibitor, the anilino group was angled out of plane and was positioned between Lys-53 and Thr-106 in a manner similar to that observed for the aryl substituent of the pyridinylimidazole class of inhibitor. | ||
==About this Structure== | ==About this Structure== | ||
1DI8 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 DTQ as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1DI8 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=DTQ:'>DTQ</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DI8 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Hassell, A.]] | [[Category: Hassell, A.]] | ||
[[Category: Kuyper, L | [[Category: Kuyper, L F.]] | ||
[[Category: Shewchuk, L.]] | [[Category: Shewchuk, L.]] | ||
[[Category: DTQ]] | [[Category: DTQ]] | ||
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[[Category: serine/threonine protein kinase]] | [[Category: serine/threonine protein kinase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:16:47 2008'' | ||
Revision as of 13:16, 21 February 2008
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THE STRUCTURE OF CYCLIN-DEPENDENT KINASE 2 (CDK2) IN COMPLEX WITH 4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE
OverviewOverview
4-Anilinoquinazolines represent an important class of protein kinase inhibitor. Modes of binding for two members of this inhibitor class were determined by X-ray crystallographic analysis of one inhibitor (4-[3-hydroxyanilino]-6,7-dimethoxyquinazoline) in complex with cyclin-dependent kinase 2 (CDK2) and the other (4-[3-methylsulfanylanilino]-6,7-dimethoxyquinazoline) in complex with p38 kinase. In both inhibitor/kinase structures, the 4-anilinoquinazoline was bound in the ATP site with the quinazoline ring system oriented along the peptide strand that links the two domains of the protein and with the anilino substituent projecting into a hydrophobic pocket within the protein interior. In each case, the nitrogen at position-1 of the quinazoline accepted a hydrogen bond from a backbone NH (CDK2, Leu-83; p38, Met-109) of the domain connector strand, and aromatic hydrogen atoms at C2 and C8 interacted with backbone carbonyl oxygen atoms of the peptide strand. The anilino group of the CDK2-bound compound was essentially coplanar with the quinazoline ring system and occupied a pocket between Lys-33 and Phe-80. For the p38-bound inhibitor, the anilino group was angled out of plane and was positioned between Lys-53 and Thr-106 in a manner similar to that observed for the aryl substituent of the pyridinylimidazole class of inhibitor.
About this StructureAbout this Structure
1DI8 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase., Shewchuk L, Hassell A, Wisely B, Rocque W, Holmes W, Veal J, Kuyper LF, J Med Chem. 2000 Jan 13;43(1):133-8. PMID:10633045
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