1lqb
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1lqb |SIZE=350|CAPTION= <scene name='initialview01'>1lqb</scene>, resolution 2.00Å | |PDB= 1lqb |SIZE=350|CAPTION= <scene name='initialview01'>1lqb</scene>, resolution 2.00Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | + | |LIGAND= <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lqb OCA], [http://www.ebi.ac.uk/pdbsum/1lqb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lqb RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
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. | 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== | ||
| - | Known diseases associated with this structure: Hemangioblastoma, cerebellar, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608537 608537]], Pheochromocytoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608537 608537]], Polycythemia, benign familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608537 608537]], Renal cell carcinoma, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608537 608537]], von Hippel-Lindau syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608537 608537]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 35: | Line 35: | ||
[[Category: Stuart, D I.]] | [[Category: Stuart, D I.]] | ||
[[Category: Wilson, M I.]] | [[Category: Wilson, M I.]] | ||
| - | [[Category: SO4]] | ||
[[Category: cancer]] | [[Category: cancer]] | ||
[[Category: prolyl hydroxylation]] | [[Category: prolyl hydroxylation]] | ||
| Line 43: | Line 42: | ||
[[Category: ubiquitin]] | [[Category: ubiquitin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:06:01 2008'' |
Revision as of 19:06, 30 March 2008
| |||||||
| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of a hydroxylated HIF-1 alpha peptide bound to the pVHL/elongin-C/elongin-B complex
Overview
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.
About this Structure
1LQB is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Sun Mar 30 22:06:01 2008
Categories: Homo sapiens | Protein complex | Claridge, T D. | Harlos, K. | Hon, W C. | Jones, E Y. | Maxwell, P H. | Pugh, C W. | Ratcliffe, P J. | Schofield, C J. | Stuart, D I. | Wilson, M I. | Cancer | Prolyl hydroxylation | Protein-peptide complex | Proteosomal degradation | Tumor suppressor | Ubiquitin
