2zgd
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | [[Image:2zgd. | + | {{Seed}} |
| + | [[Image:2zgd.png|left|200px]] | ||
<!-- | <!-- | ||
| Line 9: | Line 10: | ||
{{STRUCTURE_2zgd| PDB=2zgd | SCENE= }} | {{STRUCTURE_2zgd| PDB=2zgd | SCENE= }} | ||
| - | + | ===Asn-hydroxylation stabilises the ankyrin repeat domain fold=== | |
| - | |||
| - | ==Overview== | ||
| - | The stability and activity of hypoxia-inducible factor (HIF) are regulated by the post-translational hydroxylation of specific prolyl and asparaginyl residues. We show that the HIF asparaginyl hydroxylase, factor inhibiting HIF (FIH), also catalyzes hydroxylation of highly conserved asparaginyl residues within ankyrin repeat (AR) domains (ARDs) of endogenous Notch receptors. AR hydroxylation decreases the extent of ARD binding to FIH while not affecting signaling through the canonical Notch pathway. ARD proteins were found to efficiently compete with HIF for FIH-dependent hydroxylation. Crystallographic analyses of the hydroxylated Notch ARD (2.35A) and of Notch peptides bound to FIH (2.4-2.6A) reveal the stereochemistry of hydroxylation on the AR and imply that significant conformational changes are required in the ARD fold in order to enable hydroxylation at the FIH active site. We propose that ARD proteins function as natural inhibitors of FIH and that the hydroxylation status of these proteins provides another oxygen-dependent interface that modulates HIF signaling. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2ZGD is a | + | 2ZGD is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZGD OCA]. |
==Reference== | ==Reference== | ||
| - | + | <ref group="xtra">PMID:17573339</ref><ref group="xtra">PMID:17003112</ref><references group="xtra"/> | |
| - | + | ||
[[Category: McDonough, M A.]] | [[Category: McDonough, M A.]] | ||
[[Category: Schofield, C J.]] | [[Category: Schofield, C J.]] | ||
| Line 26: | Line 23: | ||
[[Category: De novo protein]] | [[Category: De novo protein]] | ||
[[Category: Hydroxylated]] | [[Category: Hydroxylated]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
| + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 10:12:14 2009'' | ||
Revision as of 08:12, 18 February 2009
Asn-hydroxylation stabilises the ankyrin repeat domain fold
About this Structure
2ZGD is a 1 chain structure. Full crystallographic information is available from OCA.
Reference
- Coleman ML, McDonough MA, Hewitson KS, Coles C, Mecinovic J, Edelmann M, Cook KM, Cockman ME, Lancaster DE, Kessler BM, Oldham NJ, Ratcliffe PJ, Schofield CJ. Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor. J Biol Chem. 2007 Aug 17;282(33):24027-38. Epub 2007 Jun 15. PMID:17573339 doi:http://dx.doi.org/10.1074/jbc.M704102200
- Cockman ME, Lancaster DE, Stolze IP, Hewitson KS, McDonough MA, Coleman ML, Coles CH, Yu X, Hay RT, Ley SC, Pugh CW, Oldham NJ, Masson N, Schofield CJ, Ratcliffe PJ. Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH). Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14767-72. Epub 2006 Sep 26. PMID:17003112
Page seeded by OCA on Wed Feb 18 10:12:14 2009
