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PDBsum entry 2zgd
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protein metals links
De novo protein PDB id
2zgd

 

 

 

 

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Contents
Protein chain
97 a.a. *
Metals
_CL ×2
_CD ×5
Waters ×77
* Residue conservation analysis
PDB id:
2zgd
Name: De novo protein
Title: Asn-hydroxylation stabilises the ankyrin repeat domain fold
Structure: 3 repeat synthetic ankyrin. Chain: a. Engineered: yes
Source: Synthetic: yes. Other_details: synthetically designed construct
Resolution:
1.90Å     R-factor:   0.173     R-free:   0.224
Authors: M.A.Mcdonough,C.J.Schofield
Key ref: L.Kelly et al. (2009). Asparagine beta-hydroxylation stabilizes the ankyrin repeat domain fold. Mol Biosyst, 5, 52-58. PubMed id: 19081931
Date:
21-Jan-08     Release date:   05-Feb-08    
PROCHECK
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 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 97 a.a.
Key:    Secondary structure  CATH domain

 

 
Mol Biosyst 5:52-58 (2009)
PubMed id: 19081931  
 
 
Asparagine beta-hydroxylation stabilizes the ankyrin repeat domain fold.
L.Kelly, M.A.McDonough, M.L.Coleman, P.J.Ratcliffe, C.J.Schofield.
 
  ABSTRACT  
 
Ankyrin repeats (ARs) are one of the most common structural motifs among eukaryotic proteins. Recent analyses have shown that factor inhibiting hypoxia-inducible factor (FIH) catalyses the hydroxylation of highly conserved Asn-residues within ankyrin repeat domains (ARDs). However, the effect of Asn-hydroxylation on ARD structure is unknown. Supporting the proposal that FIH-mediated ARD hydroxylation is ubiquitous we report that consensus ARD proteins are FIH substrates both in vitro and in vivo. X-ray diffraction analyses revealed that hydroxylation does not alter the archetypical ARD conformation in the crystalline state. However, other biophysical analyses revealed that hydroxylation significantly stabilizes the ARD fold in solution. We propose that intracellular protein hydroxylation is much more common than previously thought and that one of its roles is stabilization of localized regions of ARD folds.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20728359 C.Loenarz, and C.J.Schofield (2011).
Physiological and biochemical aspects of hydroxylations and demethylations catalyzed by human 2-oxoglutarate oxygenases.
  Trends Biochem Sci, 36, 7.  
  21251231 M.Yang, R.Chowdhury, W.Ge, R.B.Hamed, M.A.McDonough, T.D.Claridge, B.M.Kessler, M.E.Cockman, P.J.Ratcliffe, and C.J.Schofield (2011).
Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains.
  FEBS J, 278, 1086-1097.
PDB code: 2y0i
21177872 M.Yang, W.Ge, R.Chowdhury, T.D.Claridge, H.B.Kramer, B.Schmierer, M.A.McDonough, L.Gong, B.M.Kessler, P.J.Ratcliffe, M.L.Coleman, and C.J.Schofield (2011).
Asparagine and Aspartate Hydroxylation of the Cytoskeletal Ankyrin Family Is Catalyzed by Factor-inhibiting Hypoxia-inducible Factor.
  J Biol Chem, 286, 7648-7660.
PDB code: 2xum
20955552 B.Schmierer, B.Novák, and C.J.Schofield (2010).
Hypoxia-dependent sequestration of an oxygen sensor by a widespread structural motif can shape the hypoxic response--a predictive kinetic model.
  BMC Syst Biol, 4, 139.  
19843542 C.Loenarz, W.Ge, M.L.Coleman, N.R.Rose, C.D.Cooper, R.J.Klose, P.J.Ratcliffe, and C.J.Schofield (2010).
PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an Nepsilon-dimethyl lysine demethylase.
  Hum Mol Genet, 19, 217-222.  
20055761 E.Flashman, S.L.Davies, K.K.Yeoh, and C.J.Schofield (2010).
Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents.
  Biochem J, 427, 135-142.  
19754349 S.Nagel, N.P.Talbot, J.Mecinović, T.G.Smith, A.M.Buchan, and C.J.Schofield (2010).
Therapeutic manipulation of the HIF hydroxylases.
  Antioxid Redox Signal, 12, 481-501.  
19245366 J.D.Webb, A.Murányi, C.W.Pugh, P.J.Ratcliffe, and M.L.Coleman (2009).
MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH).
  Biochem J, 420, 327-333.  
18936059 M.E.Cockman, J.D.Webb, H.B.Kramer, B.M.Kessler, and P.J.Ratcliffe (2009).
Proteomics-based identification of novel factor inhibiting hypoxia-inducible factor (FIH) substrates indicates widespread asparaginyl hydroxylation of ankyrin repeat domain-containing proteins.
  Mol Cell Proteomics, 8, 535-546.  
19845602 M.E.Cockman, J.D.Webb, and P.J.Ratcliffe (2009).
FIH-dependent asparaginyl hydroxylation of ankyrin repeat domain-containing proteins.
  Ann N Y Acad Sci, 1177, 9.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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