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PDBsum entry 2v4a
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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2v4a

 

 

 

 

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Contents
Protein chains
182 a.a. *
187 a.a. *
194 a.a. *
Ligands
GOL ×4
SO4
DMS ×2
Metals
_CL ×4
Waters ×313
* Residue conservation analysis
PDB id:
2v4a
Name: Hydrolase
Title: Crystal structure of the semet-labeled prolyl-4 hydroxylase (p4h) type i from green algae chlamydomonas reinhardtii.
Structure: Prolyl-4 hydroxylase. Chain: a, b, c, d. Engineered: yes. Other_details: n-terminally truncated construct starting from val-29 and containing n-terminal his-tag
Source: Chlamydomonas reinhardtii. Organism_taxid: 3055. Strain: cc125mt137c. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.93Å     R-factor:   0.192     R-free:   0.223
Authors: M.K.Koski,R.Hieta,C.Bollner,K.I.Kivirikko,J.Myllyharju,R.K.Wierenga
Key ref:
M.K.Koski et al. (2007). The active site of an algal prolyl 4-hydroxylase has a large structural plasticity. J Biol Chem, 282, 37112-37123. PubMed id: 17940281 DOI: 10.1074/jbc.M706554200
Date:
28-Jun-07     Release date:   30-Oct-07    
PROCHECK
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 Headers
 References

Protein chains
No UniProt id for this chain
Struc: 182 a.a.
Protein chain
No UniProt id for this chain
Struc: 187 a.a.
Protein chain
No UniProt id for this chain
Struc: 194 a.a.
Key:    Secondary structure  CATH domain

 

 
DOI no: 10.1074/jbc.M706554200 J Biol Chem 282:37112-37123 (2007)
PubMed id: 17940281  
 
 
The active site of an algal prolyl 4-hydroxylase has a large structural plasticity.
M.K.Koski, R.Hieta, C.Böllner, K.I.Kivirikko, J.Myllyharju, R.K.Wierenga.
 
  ABSTRACT  
 
Prolyl 4-hydroxylases (P4Hs) are 2-oxoglutarate dioxygenases that catalyze the hydroxylation of peptidyl prolines. They play an important role in collagen synthesis, oxygen homeostasis, and plant cell wall formation. We describe four structures of a P4H from the green alga Chlamydomonas reinhardtii, two of the apoenzyme at 1.93 and 2.90A resolution, one complexed with the competitive inhibitor Zn(2+), and one with Zn(2+) and pyridine 2,4-dicarboxylate (which is an analogue of 2-oxoglutarate) at 1.85A resolution. The structures reveal the double-stranded beta-helix core fold (jellyroll motif), typical for 2-oxoglutarate dioxygenases. The catalytic site is at the center of an extended shallow groove lined by two flexible loops. Mutagenesis studies together with the crystallographic data indicate that this groove participates in the binding of the proline-rich peptide-substrates. It is discussed that the algal P4H and the catalytic domain of collagen P4Hs have notable structural similarities, suggesting that these enzymes form a separate structural subgroup of P4Hs different from the hypoxia-inducible factor P4Hs. Key structural differences between these two subgroups are described. These studies provide first insight into the structure-function relationships of the collagen P4Hs, which unlike the hypoxia-inducible factor P4Hs use proline-rich peptides as their substrates.
 
  Selected figure(s)  
 
Figure 1.
FIGURE 1. The reaction catalyzed by P4H (A) and the structures of 2-oxoglutarate (B) and pyridine 2,4-dicarboxylate (C). For consistency in nomenclature, the atoms in pyridine 2,4-dicarboxylate are shown using the same numbering as in 2-oxoglutarate. 		Figure 8.
FIGURE 8. Stereoviews of the superimposition of the catalytic sites of the ternary structures of Cr-P4H-1, HIF-P4H-2, and CAS. A, stereo view showing the active site of the ternary structure of Cr-P4H-1 superimposed on that of HIF-P4H-2 complexed with inhibitor and Fe^2+ (PDB code 2G19). B, superimposition of the ternary Cr-P4H-1 active site with the CAS active site complexed with Fe^2+ and 2-oxoglutarate in the presence or absence of NO. The Cr-P4H-1 is shown with gray carbons and bonds in both panels. In panel A HIF-P4H-2 and the bound inhibitor are in cyan. In panel B CAS is shown in yellow, whereas the two modes of binding of 2-oxoglutarate are in yellow (in the complex without NO; PDB code 1DRY) and magenta (in the complex with NO, PDB code 1GVG). The water molecules in the active sites of HIF-P4H-2 (two waters) and CAS (one water in the structure with NO) are shown in magenta.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 37112-37123) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22343896 P.Koivunen, S.Lee, C.G.Duncan, G.Lopez, G.Lu, S.Ramkissoon, J.A.Losman, P.Joensuu, U.Bergmann, S.Gross, J.Travins, S.Weiss, R.Looper, K.L.Ligon, R.G.Verhaak, H.Yan, and W.G.Kaelin (2012).
Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation.
  Nature, 483, 484-488.  
21404419 R.Mazmouz, F.Chapuis-Hugon, V.Pichon, A.Méjean, and O.Ploux (2011).
The Last Step of the Biosynthesis of the Cyanotoxins Cylindrospermopsin and 7-epi-Cylindrospermopsin is Catalysed by CyrI, a 2-Oxoglutarate-Dependent Iron Oxygenase.
  Chembiochem, 12, 858-862.  
20040577 H.S.Kim, H.L.Kim, K.H.Kim, d.o. .J.Kim, S.J.Lee, J.Y.Yoon, H.J.Yoon, H.Y.Lee, S.B.Park, S.J.Kim, J.Y.Lee, and S.W.Suh (2010).
Crystal structure of Tpa1 from Saccharomyces cerevisiae, a component of the messenger ribonucleoprotein complex.
  Nucleic Acids Res, 38, 2099-2110.
PDB codes: 3kt1 3kt4 3kt7
20199358 K.L.Gorres, and R.T.Raines (2010).
Prolyl 4-hydroxylase.
  Crit Rev Biochem Mol Biol, 45, 106-124.  
20498719 K.Reuter, M.Pittelkow, J.Bursy, A.Heine, T.Craan, and E.Bremer (2010).
Synthesis of 5-hydroxyectoine from ectoine: crystal structure of the non-heme iron(II) and 2-oxoglutarate-dependent dioxygenase EctD.
  PLoS One, 5, e10647.
PDB code: 3emr
19947658 M.A.Culpepper, E.E.Scott, and J.Limburg (2010).
Crystal structure of prolyl 4-hydroxylase from Bacillus anthracis.
  Biochemistry, 49, 124-133.
PDB code: 3itq
19762917 M.Hyry, J.Lantto, and J.Myllyharju (2009).
Missense mutations that cause Bruck syndrome affect enzymatic activity, folding, and oligomerization of lysyl hydroxylase 2.
  J Biol Chem, 284, 30917-30924.  
19553701 M.K.Koski, R.Hieta, M.Hirsilä, A.Rönkä, J.Myllyharju, and R.K.Wierenga (2009).
The crystal structure of an algal prolyl 4-hydroxylase complexed with a proline-rich peptide reveals a novel buried tripeptide binding motif.
  J Biol Chem, 284, 25290-25301.
PDB code: 3gze
19604478 R.Chowdhury, M.A.McDonough, J.Mecinović, C.Loenarz, E.Flashman, K.S.Hewitson, C.Domene, and C.J.Schofield (2009).
Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases.
  Structure, 17, 981-989.
PDB codes: 3hqr 3hqu
19604469 T.D.Bugg (2009).
Oxygenases get to grips with polypeptides.
  Structure, 17, 913-914.  
  18765905 M.A.Miller, E.E.Scott, and J.Limburg (2008).
Expression, purification, crystallization and preliminary X-ray studies of a prolyl-4-hydroxylase protein from Bacillus anthracis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 788-791.  
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 codes are shown on the right.

 

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