1lqb: Difference between revisions
New page: left|200px<br /> <applet load="1lqb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lqb, resolution 2.00Å" /> '''Crystal structure o... |
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[[Image:1lqb.gif|left|200px]]<br /> | [[Image:1lqb.gif|left|200px]]<br /><applet load="1lqb" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1lqb, resolution 2.00Å" /> | caption="1lqb, resolution 2.00Å" /> | ||
'''Crystal structure of a hydroxylated HIF-1 alpha peptide bound to the pVHL/elongin-C/elongin-B complex'''<br /> | '''Crystal structure of a hydroxylated HIF-1 alpha peptide bound to the pVHL/elongin-C/elongin-B complex'''<br /> | ||
==Overview== | ==Overview== | ||
Hypoxia-inducible factor-1 (HIF-1) is a transcriptional complex that | Hypoxia-inducible factor-1 (HIF-1) is a transcriptional complex that controls cellular and systemic homeostatic responses to oxygen availability. HIF-1 alpha is the oxygen-regulated subunit of HIF-1, an alpha beta heterodimeric complex. HIF-1 alpha is stable in hypoxia, but in the presence of oxygen it is targeted for proteasomal degradation by the ubiquitination complex pVHL, the protein of the von Hippel Lindau (VHL) tumour suppressor gene and a component of an E3 ubiquitin ligase complex. Capture of HIF-1 alpha by pVHL is regulated by hydroxylation of specific prolyl residues in two functionally independent regions of HIF-1 alpha. The crystal structure of a hydroxylated HIF-1 alpha peptide bound to VCB (pVHL, elongins C and B) and solution binding assays reveal a single, conserved hydroxyproline-binding pocket in pVHL. Optimized hydrogen bonding to the buried hydroxyprolyl group confers precise discrimination between hydroxylated and unmodified prolyl residues. This mechanism provides a new focus for development of therapeutic agents to modulate cellular responses to hypoxia. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1LQB is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1LQB is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LQB OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Claridge, T | [[Category: Claridge, T D.]] | ||
[[Category: Harlos, K.]] | [[Category: Harlos, K.]] | ||
[[Category: Hon, W | [[Category: Hon, W C.]] | ||
[[Category: Jones, E | [[Category: Jones, E Y.]] | ||
[[Category: Maxwell, P | [[Category: Maxwell, P H.]] | ||
[[Category: Pugh, C | [[Category: Pugh, C W.]] | ||
[[Category: Ratcliffe, P | [[Category: Ratcliffe, P J.]] | ||
[[Category: Schofield, C | [[Category: Schofield, C J.]] | ||
[[Category: Stuart, D | [[Category: Stuart, D I.]] | ||
[[Category: Wilson, M | [[Category: Wilson, M I.]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: cancer]] | [[Category: cancer]] | ||
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[[Category: ubiquitin]] | [[Category: ubiquitin]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:47:26 2008'' | ||
Revision as of 14:47, 21 February 2008
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Crystal structure of a hydroxylated HIF-1 alpha peptide bound to the pVHL/elongin-C/elongin-B complex
OverviewOverview
Hypoxia-inducible factor-1 (HIF-1) is a transcriptional complex that controls cellular and systemic homeostatic responses to oxygen availability. HIF-1 alpha is the oxygen-regulated subunit of HIF-1, an alpha beta heterodimeric complex. HIF-1 alpha is stable in hypoxia, but in the presence of oxygen it is targeted for proteasomal degradation by the ubiquitination complex pVHL, the protein of the von Hippel Lindau (VHL) tumour suppressor gene and a component of an E3 ubiquitin ligase complex. Capture of HIF-1 alpha by pVHL is regulated by hydroxylation of specific prolyl residues in two functionally independent regions of HIF-1 alpha. The crystal structure of a hydroxylated HIF-1 alpha peptide bound to VCB (pVHL, elongins C and B) and solution binding assays reveal a single, conserved hydroxyproline-binding pocket in pVHL. Optimized hydrogen bonding to the buried hydroxyprolyl group confers precise discrimination between hydroxylated and unmodified prolyl residues. This mechanism provides a new focus for development of therapeutic agents to modulate cellular responses to hypoxia.
DiseaseDisease
Known diseases associated with this structure: Hemangioblastoma, cerebellar, somatic OMIM:[608537], Pheochromocytoma OMIM:[608537], Polycythemia, benign familial OMIM:[608537], Renal cell carcinoma, somatic OMIM:[608537], von Hippel-Lindau syndrome OMIM:[608537]
About this StructureAbout this Structure
1LQB is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL., Hon WC, Wilson MI, Harlos K, Claridge TD, Schofield CJ, Pugh CW, Maxwell PH, Ratcliffe PJ, Stuart DI, Jones EY, Nature. 2002 Jun 27;417(6892):975-8. Epub 2002 Jun 5. PMID:12050673
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