1lm8: Difference between revisions

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|PDB= 1lm8 |SIZE=350|CAPTION= <scene name='initialview01'>1lm8</scene>, resolution 1.85&Aring;
|PDB= 1lm8 |SIZE=350|CAPTION= <scene name='initialview01'>1lm8</scene>, resolution 1.85&Aring;
|SITE=  
|SITE=  
|LIGAND=  
|LIGAND= <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>
|ACTIVITY=  
|ACTIVITY=  
|GENE=  
|GENE=  
|DOMAIN=
|RELATEDENTRY=
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lm8 OCA], [http://www.ebi.ac.uk/pdbsum/1lm8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lm8 RCSB]</span>
}}
}}


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==Overview==
==Overview==
The ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor suppressor (pVHL) plays a central role in the cellular response to changes in oxygen availability. pVHL binds to HIF only when a conserved proline in HIF is hydroxylated, a modification that is oxygen-dependent. The 1.85 angstrom structure of a 20-residue HIF-1alpha peptide-pVHL-ElonginB-ElonginC complex shows that HIF-1alpha binds to pVHL in an extended beta strand-like conformation. The hydroxyproline inserts into a gap in the pVHL hydrophobic core, at a site that is a hotspot for tumorigenic mutations, with its 4-hydroxyl group recognized by buried serine and histidine residues. Although the beta sheet-like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling.
The ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor suppressor (pVHL) plays a central role in the cellular response to changes in oxygen availability. pVHL binds to HIF only when a conserved proline in HIF is hydroxylated, a modification that is oxygen-dependent. The 1.85 angstrom structure of a 20-residue HIF-1alpha peptide-pVHL-ElonginB-ElonginC complex shows that HIF-1alpha binds to pVHL in an extended beta strand-like conformation. The hydroxyproline inserts into a gap in the pVHL hydrophobic core, at a site that is a hotspot for tumorigenic mutations, with its 4-hydroxyl group recognized by buried serine and histidine residues. Although the beta sheet-like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling.
==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==
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[[Category: tumor suppressor]]
[[Category: tumor suppressor]]


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